www.Cancer-Genetics.org
Navigate
HSP90AB1; heat shock protein 90kDa alpha (cytosolic), class B member 1 (6p12)

Gene Summary

Gene:HSP90AB1; heat shock protein 90kDa alpha (cytosolic), class B member 1
Aliases: HSP84, HSPC2, HSPCB, D6S182, HSP90B
Location:6p12
Summary:This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Dec 2012]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:heat shock protein HSP 90-beta
HPRD
Source:NCBI
Updated:14 December, 2014

Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 14 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • EIF4E
  • 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
  • Polymerase Chain Reaction
  • Stomach Cancer
  • Eukaryotic Initiation Factor-4G
  • Messenger RNA
  • Lung Cancer
  • HSP90 Heat-Shock Proteins
  • Caenorhabditis elegans
  • ERBB2
  • Viral Regulatory and Accessory Proteins
  • Ovarian Cancer
  • 7-tosylcyclonovobiocic acid
  • Oncogene Proteins
  • Annexin A1
  • Acute Myeloid Leukaemia
  • Biological Models
  • DNA-Binding Proteins
  • Phosphorylation
  • Cancer Gene Expression Regulation
  • Gemcitabine
  • Apoptosis
  • Alleles
  • Transcription Factors
  • Single Nucleotide Polymorphism
  • Valproic Acid
  • Benzoquinones
  • Up-Regulation
  • Deoxycytidine
  • Immunohistochemistry
  • Non-Small Cell Lung Cancer
  • Tumor Suppressor Proteins
  • TOR Serine-Threonine Kinases
  • Chromosome 6
  • Base Sequence
  • Ribosomal Proteins
  • cdc25 Phosphatases
  • Cell Cycle Proteins
  • Young Adult
  • Lymphatic Metastasis
Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (5)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Lung CancerHSP90AB1 and Lung Cancer View Publications3
Lung Cancer, Non-Small CellHSP90AB1 and Non-Small Cell Lung Cancer View Publications2
Stomach CancerHSP90AB1 and Stomach Cancer View Publications1
Acute Myeloid Leukaemia (AML)HSP90AB1 and Acute Myeloid Leukaemia View Publications1
Ovarian CancerHSP90AB1 and Ovarian Cancer View Publications1

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Related Links

Latest Publications: HSP90AB1 (cancer-related)

Coskunpinar E, Akkaya N, Yildiz P, et al.
The significance of HSP90AA1, HSP90AB1 and HSP90B1 gene polymorphisms in a Turkish population with non-small cell lung cancer.
Anticancer Res. 2014; 34(2):753-7 [PubMed] Related Publications
BACKGROUND/AIM: Heat-shock proteins (HSPs) are molecular chaperones which modify the structures and interactions of other proteins. The aim of our study was to investigate HSP90AA1, HSP90AB1 and HSP90B1 gene polymorphisms in patients with non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS: Ninety-seven patients with NSCLC and 97 healthy controls were included in the study. Real-time polymerase chain reaction was used for genotyping.
RESULTS: The frequency of mutant CC genotype for HSP90AA1 (rs4947C/T), mutant AA genotype for HSP90AB1 (rs13296A/G) and mutant CC genotype for HSP90B1 (rs2070908 C/G) was significantly higher in the patient group than in controls (p=0.019, p=0.004 and p=0.036, respectively). The frequency of patients with homozygote mutant allele was also significantly higher than that of controls and possessing of the mutant genotype increased the risk for disease by approximately 2.9, 4.8, 1.9 for HSP90AA1, HSP90AB1 and HSP90B1, respectively. The present study appears to be the first of its kind to report data on these gene polymorphisms in patients with NSCLC in the Turkish population.

Related: Non-Small Cell Lung Cancer Lung Cancer


Tanaka K, Eskin A, Chareyre F, et al.
Therapeutic potential of HSP90 inhibition for neurofibromatosis type 2.
Clin Cancer Res. 2013; 19(14):3856-70 [PubMed] Related Publications
PURPOSE: The growth and survival of neurofibromatosis type 2 (NF2)-deficient cells are enhanced by the activation of multiple signaling pathways including ErbBs/IGF-1R/Met, PI3K/Akt, and Ras/Raf/Mek/Erk1/2. The chaperone protein HSP90 is essential for the stabilization of these signaling molecules. The aim of the study was to characterize the effect of HSP90 inhibition in various NF2-deficient models.
EXPERIMENTAL DESIGN: We tested efficacy of the small-molecule NXD30001, which has been shown to be a potent HSP90 inhibitor. The antiproliferative activity of NXD30001 was tested in NF2-deficient cell lines and in human primary schwannoma and meningioma cultures in vitro. The antitumor efficacy of HSP90 inhibition in vivo was verified in two allograft models and in one NF2 transgenic model. The underlying molecular alteration was further characterized by a global transcriptome approach.
RESULTS: NXD30001 induced degradation of client proteins in and suppressed proliferation of NF2-deficient cells. Differential expression analysis identified subsets of genes implicated in cell proliferation, cell survival, vascularization, and Schwann cell differentiation whose expression was altered by NXD30001 treatment. The results showed that NXD30001 in NF2-deficient schwannoma suppressed multiple pathways necessary for tumorigenesis.
CONCLUSIONS: HSP90 inhibition showing significant antitumor activity against NF2-related tumor cells in vitro and in vivo represents a promising option for novel NF2 therapies.


Forthun RB, Sengupta T, Skjeldam HK, et al.
Cross-species functional genomic analysis identifies resistance genes of the histone deacetylase inhibitor valproic acid.
PLoS One. 2012; 7(11):e48992 [PubMed] Free Access to Full Article Related Publications
The mechanisms of successful epigenetic reprogramming in cancer are not well characterized as they involve coordinated removal of repressive marks and deposition of activating marks by a large number of histone and DNA modification enzymes. Here, we have used a cross-species functional genomic approach to identify conserved genetic interactions to improve therapeutic effect of the histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in more than 20% of patients with advanced acute myeloid leukemia (AML). Using a bidirectional synthetic lethality screen revealing genes that increased or decreased VPA sensitivity in C. elegans, we identified novel conserved sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which demonstrates a functional relationship between protein acetylation and lysine-specific methylation. The synthetic lethal screen identified resistance programs that compensated for the HDACi-induced global hyper-acetylation, and confirmed MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs represent promising novel targets for refinement of combinatorial epigenetic anti-cancer therapy.

Related: Acute Myeloid Leukemia (AML)


Giessrigl B, Krieger S, Rosner M, et al.
Hsp90 stabilizes Cdc25A and counteracts heat shock-mediated Cdc25A degradation and cell-cycle attenuation in pancreatic carcinoma cells.
Hum Mol Genet. 2012; 21(21):4615-27 [PubMed] Related Publications
Pancreas cancer cells escape most treatment options. Heat shock protein (Hsp)90 is frequently over-expressed in pancreas carcinomas and protects a number of cell-cycle regulators such as the proto-oncogene Cdc25A. We show that inhibition of Hsp90 with geldanamycin (GD) destabilizes Cdc25A independent of Chk1/2, whereas the standard drug for pancreas carcinoma treatment, gemcitabine (GEM), causes Cdc25A degradation through the activation of Chk2. Both agents applied together additively inhibit the expression of Cdc25A and the proliferation of pancreas carcinoma cells thereby demonstrating that both Cdc25A-destabilizing/degrading pathways are separated. The role of Hsp90 as stabilizer of Cdc25A in pancreas carcinoma cells is further supported by two novel synthetic inhibitors 4-tosylcyclonovobiocic acid and 7-tosylcyclonovobiocic acid and specific Hsp90AB1 (Hsp90β) shRNA. Our data show that targeting Hsp90 reduced the resistance of pancreas carcinoma cells to treatment with GEM.

Related: CHEK2 Cancer of the Pancreas Pancreatic Cancer Gemcitabine


Thoreen CC, Chantranupong L, Keys HR, et al.
A unifying model for mTORC1-mediated regulation of mRNA translation.
Nature. 2012; 485(7396):109-13 [PubMed] Free Access to Full Article Related Publications
The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses. mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2). Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5' untranslated region length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.

Related: EIF4E Prostate Cancer


Cheng Q, Chang JT, Geradts J, et al.
Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.
Breast Cancer Res. 2012; 14(2):R62 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Although human epidermal growth factor receptor 2 (HER2) positive or estrogen receptor (ER) positive breast cancers are treated with clinically validated anti-HER2 or anti-estrogen therapies, intrinsic and acquired resistance to these therapies appears in a substantial proportion of breast cancer patients and new therapies are needed. Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer.
METHODS: We compiled a collection of 4,010 breast tumor gene expression data derived from 23 datasets that have been posted on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We performed a genome-scale survival analysis using Cox-regression survival analyses, and validated using Kaplan-Meier Estimates survival and Cox Proportional-Hazards Regression survival analyses. We conducted a genome-scale analysis of chromosome alteration using 481 breast cancer samples obtained from The Cancer Genome Atlas (TCGA), from which combined expression and copy number data were available. We assessed the correlation between somatic copy number alterations and gene expression using analysis of variance (ANOVA).
RESULTS: Increased expression of each of the heat shock protein (HSP) 90 isoforms, as well as HSP transcriptional factor 1 (HSF1), was correlated with poor prognosis in different subtypes of breast cancer. High-level expression of HSP90AA1 and HSP90AB1, two cytoplasmic HSP90 isoforms, was driven by chromosome coding region amplifications and were independent factors that led to death from breast cancer among patients with triple-negative (TNBC) and HER2-/ER+ subtypes, respectively. Furthermore, amplification of HSF1 was correlated with higher HSP90AA1 and HSP90AB1 mRNA expression among the breast cancer cells without amplifications of these two genes. A collection of HSP90AA1, HSP90AB1 and HSF1 amplifications defined a subpopulation of breast cancer with up-regulated HSP90 gene expression, and up-regulated HSP90 expression independently elevated the risk of recurrence of TNBC and poor prognosis of HER2-/ER+ breast cancer.
CONCLUSIONS: Up-regulated HSP90 mRNA expression represents a confluence of genomic vulnerability that renders HER2 negative breast cancers more aggressive, resulting in poor prognosis. Targeting breast cancer with up-regulated HSP90 may potentially improve the effectiveness of clinical intervention in this disease.

Related: Breast Cancer


Beck HC, Petersen J, Nielsen SJ, et al.
Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat.
Electrophoresis. 2010; 31(16):2714-21 [PubMed] Related Publications
The anticancer drug belinostat is a hydroxamate histone deacetylase inhibitor that has shown significant antitumour activity in various tumour models and also in clinical trials. In this study, we utilized a proteomic approach in order to evaluate the effect of this drug on protein expression in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed 45 unique differentially expressed proteins that were identified by LC-MSMS analysis. Among these proteins, of particular interest are the downregulated proteins nucleophosmin and stratifin, and the upregulated proteins nucleolin, gelsolin, heterogeneous nuclear ribonucleoprotein K, annexin 1, and HSP90B that all were related to the proto-oncogene proteins p53, Myc, activator protein 1, and c-fos protein. The modulation of these proteins is consistent with the observations that belinostat is able to inhibit clonogenic cell growth of HCT116 cells and the biological role of these proteins will be discussed.


Fu J, Bian L, Zhao L, et al.
Identification of genes for normalization of quantitative real-time PCR data in ovarian tissues.
Acta Biochim Biophys Sin (Shanghai). 2010; 42(8):568-74 [PubMed] Related Publications
Increased attention has been paid to the determination of the potential biomarker and therapeutic target for ovarian cancer in recent years. However, the normalization of quantitative real-time PCR is important to obtain accurate gene expression data. We investigated the stability of 20 reference genes in ovarian tissues under different conditions to determine the most adequate for this application. The study characterized the expression of 20 possible reference genes among 52 ovarian tissue samples involving the normal, non-malignant, and primary ovarian carcinomas. One-way analysis of variance (ANOVA) method was used to compare the candidate gene changes brought about by the disease progression. The stability and suitability of the genes with no statistic difference were further validated employing geNorm and NormFinder softwares. Results showed that the expression levels of the 20 reference genes varied, while the RPL4, RPLP0, HSPCB, TPT1, RPL13A, 18S rRNA, PPIA, TBP, and GUSB kept statistic stability despite different ovarian tissue conditions. RPL4, RPLP0, and HSPCB were demonstrated as the most stable reference genes and the combination of the RPLP0 and RPL4 should be recommended as a much more reliable normalization strategy.

Related: Ovarian Cancer


Tsumuraya M, Kato H, Miyachi K, et al.
Comprehensive analysis of genes involved in the malignancy of gastrointestinal stromal tumors.
Anticancer Res. 2010; 30(7):2705-15 [PubMed] Related Publications
BACKGROUND: During tumorigenesis of gastrointestinal stromal tumors (GISTs), the most frequent changes are reported to be gain-of-function mutations in the C-KIT proto-oncogene. However, we speculated that additional genetic alterations are required for the progression of GISTs.
PATIENTS AND METHODS: Using 15 cases diagnosed with GISTs, we searched for novel indicator genes by microarray analyses using an Oligo GEArray(R) PI3K-AKT Signaling Pathway Microarray Kit. In addition, we analyzed the mutational status of C-KIT and the proliferation status indicated by the Ki-67 index.
RESULTS: The tumor localizations of the 15 GISTs were as follows: 8 in the stomach; 2 in the small intestine; 2 in the mesentery; 1 in the duodenum; 1 in the rectum; and 1 in liver. Regarding the C-KIT gene analysis, mutations in exon 11 were detected in 11 out of 13 patients. In 1 out of the 13 patients, mutations were detected in both exons 11 and 13. No genetic abnormalities were identified in 1 patient. The Ki-67 labeling indices were significantly lower for the low-risk and intermediate-risk groups than for the high-risk group (p=0.0440). No specific genes were overexpressed in the >1% Ki-67 group. Regarding the primary lesion sites, the following 6 genes were overexpressed in tumors in the stomach: RBL2, RHOA, SHC1, HSP90AB1, ACTB and BAS2C.
CONCLUSION: Gene analysis is currently only useful for diagnostic assessment and predicting therapeutic effects. However, it may be possible for new malignancy-related factors to be identified by comparing and investigating gene expression levels and other factors using such analyses.

Related: Gastrointestinal Stromal Tumors Liver Cancer Stomach Cancer Gastric Cancer


Li WH, Miao XH, Qi ZT, et al.
Proteomic analysis of differently expressed proteins in human hepatocellular carcinoma cell lines HepG2 with transfecting hepatitis B virus X gene.
Chin Med J (Engl). 2009; 122(1):15-23 [PubMed] Related Publications
BACKGROUND: Hepatitis B virus encoded X protein (HBx) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBx that participate in this process have been identified. We screened, by comparative proteomics method, effectors of HBx associated with hepatocarcinogenesis.
METHODS: HBx positive and negative HepG2 cells were constructed and expression patterns of cellular proteins were obtained by high resolution, two dimensional electrophoresis. Comprehensive analyses of proteins associated with hepatocellular carcinoma (HCC) were focused on the differently expressed proteins (more than two-fold increase or decrease, P < 0.05) from HBx positive and negative HepG2 cells. For peptide mass fingerprinting, protein spots with different intensity between HBx positive and negative HepG2 cells were directly cut out of gels and processed for matrix assisted, laser desorption/ionization, time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) analysis.
RESULTS: The mean number of protein spots for HBx negative and HBx positive HepG2 cells were 2095 +/- 137 and 2188 +/- 105, respectively. The analysis of paired cells showed 75 spots with significant differences in expression between HBx negative and HBx positive cells: 37 spots corresponding to 32 different proteins; 25 proteins were upregulated, 7 downregulated. We found 7 proteins not previously reported differentially expressed in HBx positive HepG2 cells. Variations in protein accumulation were confirmed for four (HSP90AB1, BCL2 associated athanogene 2, nucleophosmin and chloride intracellular channel 1) by Western blotting in HBx positive HepG2 cells.
CONCLUSIONS: Numerous effectors of HBx that may promote the development of HCC are identified, of which 7 are newly noted in HepG2 cells. Several of these effectors of HBx may help in elucidating the roles of HBx in hepatocarcinogenesis and diagnostics or targets for therapeutic intervention.


Bucci B, Misiti S, Cannizzaro A, et al.
Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation.
Anticancer Res. 2006 Nov-Dec; 26(6B):4549-57 [PubMed] Related Publications
BACKGROUND: Radiation therapy (RT) is a well established therapeutic modality for the treatment of solid tumors. In particular, post-operative RT is considered the standard treatment adjuvant to surgery since its ability to prolong median survival of patients with malignant astrocytoma has been shown; nevertheless the ionizing radiation (IR) treatment fails in a considerable number of astrocytoma patients.
MATERIALS AND METHODS: Using an ADF human astrocytoma cell line the molecular mechanisms involved in the DNA damage induced by fractionated irradiation (FIR) and single IR treatment have been investigated.
RESULTS: FIR and single IR treatment inhibited the growth of the ADF human astrocytoma cell line. FACS analysis revealed that FIR treatment, but not single IR treatment, induced growth inhibition associated with the induction of apoptosis. Apoptosis was related to caspase-3 activation and reactive oxygen species (ROS) generation. ROS formation depends on the up-regulation of the cytochrome P450 enzyme gene. On the contrary, 12.5 Gy induced necrotic cell death up-regulating the HSPD1, HSPCB, HSPCA and HSPB1 genes.
CONCLUSION: FIR treatment induced cell death through caspase-3 and ROS-mediated apoptosis.

Related: Apoptosis CASP3


Takahashi H, Nemoto T, Yoshida T, et al.
Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method.
BMC Bioinformatics. 2006; 7:399 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis and selection of treatment. To accomplish this objective, it is important to establish a sophisticated algorithm that can deal with large quantities of data such as gene expression profiles obtained by DNA microarray analysis.
RESULTS: Previously, we developed the projective adaptive resonance theory (PART) filtering method as a gene filtering method. This is one of the clustering methods that can select specific genes for each subtype. In this study, we applied the PART filtering method to analyze microarray data that were obtained from soft tissue sarcoma (STS) patients for the extraction of subtype-specific genes. The performance of the filtering method was evaluated by comparison with other widely used methods, such as signal-to-noise, significance analysis of microarrays, and nearest shrunken centroids. In addition, various combinations of filtering and modeling methods were used to extract essential subtype-specific genes. The combination of the PART filtering method and boosting--the PART-BFCS method--showed the highest accuracy. Seven genes among the 15 genes that are frequently selected by this method--MIF, CYFIP2, HSPCB, TIMP3, LDHA, ABR, and RGS3--are known prognostic marker genes for other tumors. These genes are candidate marker genes for the diagnosis of STS. Correlation analysis was performed to extract marker genes that were not selected by PART-BFCS. Sixteen genes among those extracted are also known prognostic marker genes for other tumors, and they could be candidate marker genes for the diagnosis of STS.
CONCLUSION: The procedure that consisted of two steps, such as the PART-BFCS and the correlation analysis, was proposed. The results suggest that novel diagnostic and therapeutic targets for STS can be extracted by a procedure that includes the PART filtering method.

Related: Soft Tissue Sarcomas


Asaka S, Fujimoto T, Akaishi J, et al.
Genetic prognostic index influences patient outcome for node-positive breast cancer.
Surg Today. 2006; 36(9):793-801 [PubMed] Related Publications
PURPOSE: To establish a novel genetic prognostic index among node-positive breast cancer patients.
METHODS: Using a cDNA microarray, the gene expression profiles of 20 primary breast cancers that had metastasis to four or more axillary lymph nodes were examined. Ten patients survived disease-free for more than 5 years (5S), while ten patients died of breast cancer within 5 years of surgery (5D).
RESULTS: A set of genes characterizing each group was identified. Sixteen genes were underexpressed in 5D compared to 5S, and 15 genes were underexpressed in 5S in comparison to 5D. The prognostic index (PI) was established, which could predict the postoperative outcome with five genes that were commonly underexpressed in the 5D group; these genes encoded granulin (GRN), heat shock 90 kDa protein 1 beta (HSPCB), large tumor suppressor homolog 1 (LATS1), valosin-containing protein (VCP), and LIM-and-SH3 protein1 (LASP1).
CONCLUSION: These five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.

Related: Breast Cancer


Yu X, Harris SL, Levine AJ
The regulation of exosome secretion: a novel function of the p53 protein.
Cancer Res. 2006; 66(9):4795-801 [PubMed] Related Publications
The p53 protein responds to stress signals by regulating the transcription of a variety of genes. Some of these genes encode secreted proteins that may be involved in the communication between adjacent cells. In this study, a proteomics approach was employed to identify proteins secreted by cells in a p53-dependent manner after DNA damage. In addition to the known transcriptional targets of p53, a set of proteins encoded by genes that are not transcriptional targets of p53 were found to increase in the culture medium after p53 activation. These proteins exit the cell via small, secreted vesicles called exosomes and exosome production by cells was found to be regulated by the p53 response. A p53-regulated gene product, TSAP6, was shown to enhance exosome production in cells undergoing a p53 response to stress. Thus, the p53 pathway regulates the production of exosomes into the medium and these vesicles can communicate with adjacent cells and even cells of the immune system.

Related: Apoptosis Non-Small Cell Lung Cancer Lung Cancer TP53 SERPINB5


Man TK, Lu XY, Jaeweon K, et al.
Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma.
BMC Cancer. 2004; 4:45 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Osteosarcoma is a highly malignant bone neoplasm of children and young adults. It is characterized by extremely complex karyotypes and high frequency of chromosomal amplifications. Currently, only the histological response (degree of necrosis) to therapy represent gold standard for predicting the outcome in a patient with non-metastatic osteosarcoma at the time of definitive surgery. Patients with lower degree of necrosis have a higher risk of relapse and poor outcome even after chemotherapy and complete resection of the primary tumor. Therefore, a better understanding of the underlying molecular genetic events leading to tumor initiation and progression could result in the identification of potential diagnostic and therapeutic targets.
METHODS: We used a genome-wide screening method - array based comparative genomic hybridization (array-CGH) to identify DNA copy number changes in 48 patients with osteosarcoma. We applied fluorescence in situ hybridization (FISH) to validate some of amplified clones in this study.
RESULTS: Clones showing gains (79%) were more frequent than losses (66%). High-level amplifications and homozygous deletions constitute 28.6% and 3.8% of tumor genome respectively. High-level amplifications were present in 238 clones, of which about 37% of them showed recurrent amplification. Most frequently amplified clones were mapped to 1p36.32 (PRDM16), 6p21.1 (CDC5L, HSPCB, NFKBIE), 8q24, 12q14.3 (IFNG), 16p13 (MGRN1), and 17p11.2 (PMP22 MYCD, SOX1,ELAC27). We validated some of the amplified clones by FISH from 6p12-p21, 8q23-q24, and 17p11.2 amplicons. Homozygous deletions were noted for 32 clones and only 7 clones showed in more than one case. These 7 clones were mapped to 1q25.1 (4 cases), 3p14.1 (4 cases), 13q12.2 (2 cases), 4p15.1 (2 cases), 6q12 (2 cases), 6q12 (2 cases) and 6q16.3 (2 cases).
CONCLUSIONS: This study clearly demonstrates the utility of array CGH in defining high-resolution DNA copy number changes and refining amplifications. The resolution of array CGH technology combined with human genome database suggested the possible target genes present in the gained or lost clones.

Related: Bone Cancers Chromosome 12 Chromosome 17 Chromosome 6 Chromosome 8 Osteosarcoma


Andersen CL, Jensen JL, Ørntoft TF
Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets.
Cancer Res. 2004; 64(15):5245-50 [PubMed] Related Publications
Accurate normalization is an absolute prerequisite for correct measurement of gene expression. For quantitative real-time reverse transcription-PCR (RT-PCR), the most commonly used normalization strategy involves standardization to a single constitutively expressed control gene. However, in recent years, it has become clear that no single gene is constitutively expressed in all cell types and under all experimental conditions, implying that the expression stability of the intended control gene has to be verified before each experiment. We outline a novel, innovative, and robust strategy to identify stably expressed genes among a set of candidate normalization genes. The strategy is rooted in a mathematical model of gene expression that enables estimation not only of the overall variation of the candidate normalization genes but also of the variation between sample subgroups of the sample set. Notably, the strategy provides a direct measure for the estimated expression variation, enabling the user to evaluate the systematic error introduced when using the gene. In a side-by-side comparison with a previously published strategy, our model-based approach performed in a more robust manner and showed less sensitivity toward coregulation of the candidate normalization genes. We used the model-based strategy to identify genes suited to normalize quantitative RT-PCR data from colon cancer and bladder cancer. These genes are UBC, GAPD, and TPT1 for the colon and HSPCB, TEGT, and ATP5B for the bladder. The presented strategy can be applied to evaluate the suitability of any normalization gene candidate in any kind of experimental design and should allow more reliable normalization of RT-PCR data.

Related: Bladder Cancer Bladder Cancer - Molecular Biology


Gotoh K, Nonoguchi K, Higashitsuji H, et al.
Apg-2 has a chaperone-like activity similar to Hsp110 and is overexpressed in hepatocellular carcinomas.
FEBS Lett. 2004; 560(1-3):19-24 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. We constructed subtracted cDNA libraries enriched with genes overexpressed in HCCs. Among the 17 genes identified were molecular chaperones, Hsp110, Hsp90B, and Hsp70-1. Expression of the Hsp110 family members was further analyzed, and increased transcript levels of Hsp110 and Apg-2, but not Apg-1, were found in 12 and 14, respectively, of 18 HCCs. Immunohistochemical analysis demonstrated the overexpression of the proteins in tumor cells. Apg-2 had chaperone ability similar to Hsp110 in a thermal denaturation assay using luciferase, and showed anti-apoptotic activity. These results suggest that the Hsp110 family members play important roles in hepatocarcinogenesis through their chaperoning activities.

Related: Apoptosis Liver Cancer


Contents

Found this page useful?

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. HSPCB gene, Cancer Genetics Web: http://www.cancerindex.org/geneweb/HSPCB.htm Accessed: date

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 14 December, 2014     Cancer Genetics Web, Established 1999