STEAP2

Gene Summary

Gene:STEAP2; STEAP2 metalloreductase
Aliases: STMP, IPCA1, PUMPCn, STAMP1, PCANAP1
Location:7q21.13
Summary:This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:metalloreductase STEAP2
Source:NCBIAccessed: 15 March, 2017

Ontology:

What does this gene/protein do?
Show (18)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 15 March 2017 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.

  • Polymerase Chain Reaction
  • STEAP1
  • Prostatic Neoplasms, Castration-Resistant
  • Apoptosis
  • Oxidoreductases
  • Tumor Antigens
  • Case-Control Studies
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Regulation, Developmental
  • Genetic Therapy
  • Genome, Human
  • Biomarkers, Tumor
  • Messenger RNA
  • Western Blotting
  • Cell Cycle
  • STEAP2
  • Neoplasm Proteins
  • Morpholines
  • RTPCR
  • Neoplasm Invasiveness
  • Prostate Cancer
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • HOXD10
  • Membrane Proteins
  • Prostate
  • Homeodomain Proteins
  • DNA, Complementary
  • High-Throughput Nucleotide Sequencing
  • Amino Acid Sequence
  • Transcription Factors
  • Intestinal Mucosa
  • Down-Regulation
  • Colorectal Cancer
  • COS Cells
  • Transcriptome
  • Adenocarcinoma
  • Neoplasm Recurrence, Local
  • Mutation
  • Chromosome 7
  • TNF-Related Apoptosis-Inducing Ligand
  • Stem Cells
  • Cancer Gene Expression Regulation
Tag cloud generated 15 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

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

Latest Publications: STEAP2 (cancer-related)

Sikkeland J, Sheng X, Jin Y, Saatcioglu F
STAMPing at the crossroads of normal physiology and disease states.
Mol Cell Endocrinol. 2016; 425:26-36 [PubMed] Related Publications
The six transmembrane protein of prostate (STAMP) proteins, also known as six transmembrane epithelial antigen of prostate (STEAPs), comprises three members: STAMP1-3. Their expression is regulated by a variety of stimuli, including hormones and cytokines, in varied settings and tissues with important roles in secretion and cell differentiation. In addition, they are implicated in metabolic and inflammatory diseases and cancer. Here, we review the current knowledge on the role of STAMPs in both physiological and pathological states.

Whiteland H, Spencer-Harty S, Morgan C, et al.
A role for STEAP2 in prostate cancer progression.
Clin Exp Metastasis. 2014; 31(8):909-20 [PubMed] Related Publications
Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells.

Sowalsky AG, Xia Z, Wang L, et al.
Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer.
Mol Cancer Res. 2015; 13(1):98-106 [PubMed] Free Access to Full Article Related Publications
UNLABELLED: Men with metastatic prostate cancer who are treated with androgen deprivation therapies (ADT) usually relapse within 2 to 3 years with disease that is termed castration-resistant prostate cancer (CRPC). To identify the mechanism that drives these advanced tumors, paired-end RNA-sequencing (RNA-seq) was performed on a panel of CRPC bone marrow biopsy specimens. From this genome-wide approach, mutations were found in a series of genes with prostate cancer relevance, including AR, NCOR1, KDM3A, KDM4A, CHD1, SETD5, SETD7, INPP4B, RASGRP3, RASA1, TP53BP1, and CDH1, and a novel SND1:BRAF gene fusion. Among the most highly expressed transcripts were 10 noncoding RNAs (ncRNAs), including MALAT1 and PABPC1, which are involved in RNA processing. Notably, a high percentage of sequence reads mapped to introns, which were determined to be the result of incomplete splicing at canonical splice junctions. Using quantitative PCR (qPCR), a series of genes (AR, KLK2, KLK3, STEAP2, CPSF6, and CDK19) were confirmed to have a greater proportion of unspliced RNA in CRPC specimens than in normal prostate epithelium, untreated primary prostate cancer, and cultured prostate cancer cells. This inefficient coupling of transcription and mRNA splicing suggests an overall increase in transcription or defect in splicing.
IMPLICATIONS: Inefficient splicing in advanced prostate cancer provides a selective advantage through effects on microRNA networks but may render tumors vulnerable to agents that suppress rate-limiting steps in splicing.

Ihlaseh-Catalano SM, Drigo SA, de Jesus CM, et al.
STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma.
Histopathology. 2013; 63(5):678-85 [PubMed] Related Publications
AIMS: To investigate the prognostic value of expression levels of the genes STEAP1 and STEAP2, and of STEAP1 protein, in prostate carcinomas (PCa).
METHODS AND RESULTS: STEAP1 and STEAP2 transcript levels were evaluated by RT-qPCR in samples from 35 PCa, 24 adjacent non-neoplastic prostate (AdjP) tissues, five cases of benign prostatic hyperplasia (BPH), and two histologically normal prostates (N). STEAP1 expression was assessed by immunohistochemistry in samples from 198 PCa, 76 AdjP, 22 BPH, and two N. The findings were compared with clinical and pathological parameters and patient outcome. STEAP1 and STEAP2 transcript analysis showed no differences between the groups tested. Although not significant, higher STEAP1 mRNA levels were detected in tumours with high Gleason scores and in patients who presented with biochemical recurrence (BCR). STEAP1 overexpression was detected in PCa, and was significantly associated with high-grade Gleason scores, seminal vesicle invasion, BCR, and worse outcome (metastasis or PCa-specific death). STEAP1 overexpression was significantly associated with shorter BCR-free survival. Multivariate analysis revealed that STEAP1 is an independent marker for BCR.
CONCLUSIONS: These findings provide evidence that STEAP1 is a biomarker of worse prognosis in PCa patients.

Bhatlekar S, Addya S, Salunek M, et al.
Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.
Stem Cells Dev. 2014; 23(2):167-79 [PubMed] Free Access to Full Article Related Publications
Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

Lai Y, Yu Z, Wang Y, Ye J
Identification of PCAG1 as a novel prostate cancer-associated gene.
Mol Med Rep. 2013; 7(3):755-60 [PubMed] Related Publications
The aim of the present study was to identify a new prostate cancer‑associated gene and analyze its expression pattern. Comprehensive expression analysis of expressed sequence tags (ESTs) and microarray data and serial analysis of gene expression (SAGE) were conducted to screen in silico for candidate prostate cancer‑associated genes. Reverse transcription (RT)-PCR was performed to validate prostate cancer specificity. Prostate cancer‑associated gene 1 (PCAG1) was identified. The expression of PCAG1 mRNA and protein was evaluated in common human normal tissues, common malignant tumors, prostate adenocarcinoma and paired adjacent normal prostate tissues. An immunofluorescence assay was conducted to determine the subcellular location of PCAG1. PCAG1 mRNA was absent in the 15 pooled normal tissues (including normal prostate tissue) but registered at low levels in the spleen tissue (+). By contrast, PCAG1 mRNA was significantly higher than in the adjacent normal tissues in each of the 14 cases of prostate cancer, with ~50% scoring a high degree of expression (+++). Of the 32 types of normal tissues, 29 (including normal prostate tissue) demonstrated negative PCAG1 protein staining while the remaining tissues of the adrenal gland, parathyroid gland and liver expressed low levels. While 18/20 cases of prostate adenocarcinoma showed positive expression results, PCAG1 protein expression in the remaining types of cancer was scarce when present at all; only 41/380 other cancer cases demonstrated positive results at a low level. The most substantial PCAG1-positive expression results were identified by cytoplasmic staining in 36/38 prostate adenocarcinoma cases, with 10 cases showing high expression levels, 20 showing medium levels and 6 showing low levels. In the paired adjacent normal prostate tissues, only 3/38 cases showed low level positive staining, while 35/38 cases were negative. Immunofluorescent staining of the human prostate cancer PC3 cell line showed positive PCAG1 expression results in the mitochondria. The present study demonstrated that while PCAG1 mRNA was highly expressed in prostate cancer tissues, it was almost absent in all common normal tissues and paired adjacent normal prostate tissues. Furthermore, PCAG1 protein was also highly expressed in prostate cancer tissues, while few common normal tissues, other common malignant tumors and paired adjacent normal prostate tissues had even low levels of expression. Clarification of the function and transcriptional mechanism of PCAG1 may aid the elucidation of the mechanisms of carcinogenesis and progression of prostate cancer. The unique expression pattern of PCAG1 suggests its potential in certain clinical applications.

Gomes IM, Maia CJ, Santos CR
STEAP proteins: from structure to applications in cancer therapy.
Mol Cancer Res. 2012; 10(5):573-87 [PubMed] Related Publications
The human 6-transmembrane epithelial antigen of prostate (STEAP) family comprises STEAP1, STEAP2, STEAP3, and STEAP4. All of these proteins are unique to mammals and share an innate activity as metalloreductases, indicating their importance in metal metabolism. Overall, they participate in a wide range of biologic processes, such as molecular trafficking in the endocytic and exocytic pathways and control of cell proliferation and apoptosis. STEAP1 and STEAP2 are overexpressed in several types of human cancers, namely prostate, bladder, colon, pancreas, ovary, testis, breast, cervix, and Ewing sarcoma, but their clinical significance and role in cancer cells are not clear. Still, their localization in the cell membrane and differential expression in normal and cancer tissues make STEAP proteins potential candidates as biomarkers of several cancers, as well as potential targets for new immunotherapeutic strategies for disease attenuation or treatment. This review brings together the current knowledge about each STEAP protein, giving an overview of the roles of this family of proteins in human physiology and disease, and analyzes their potential as immunotherapeutic agents in cancer research.

Wang L, Jin Y, Arnoldussen YJ, et al.
STAMP1 is both a proliferative and an antiapoptotic factor in prostate cancer.
Cancer Res. 2010; 70(14):5818-28 [PubMed] Related Publications
STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and is deregulated in prostate cancer. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, is unknown. Here, we find that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS-7 cells in vitro; conversely, small interfering RNA-mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth and, at least partially, induced cell cycle arrest. In parallel, there were alterations in cell cycle-regulatory gene expression. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. Consistently, LNCaP cells with short hairpin RNA-mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Interestingly, activation of extracellular signal-regulated kinase, which has previously been implicated in prostate cancer progression, was significantly increased on ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly downregulated on STAMP1 knockdown in LNCaP cells. In the normal prostate, STAMP1 protein is localized to the cytosol and the cell membrane of the prostate epithelial cells; furthermore, its expression is increased in prostate cancer compared with normal prostate. Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment.

Korkmaz CG, Korkmaz KS, Kurys P, et al.
Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer.
Oncogene. 2005; 24(31):4934-45 [PubMed] Related Publications
We have identified a novel gene, six transmembrane protein of prostate 2 (STAMP2), named for its high sequence similarity to the recently identified STAMP1 gene. STAMP2 displays a tissue-restricted expression with highest expression levels in placenta, lung, heart, and prostate and is predicted to code for a 459-amino acid six transmembrane protein. Using a form of STAMP2 labeled with green flourescent protein (GFP) in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP2 is primarily localized to the Golgi complex, trans-Golgi network, and the plasma membrane. STAMP2 also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1) suggesting that it may be involved in the secretory/endocytic pathways. STAMP2 expression is exquisitely androgen regulated in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Analysis of STAMP2 expression in matched normal and tumor samples microdissected from prostate cancer specimens indicates that STAMP2 is overexpressed in prostate cancer cells compared with normal prostate epithelial cells. Furthermore, ectopic expression of STAMP2 in prostate cancer cells significantly increases cell growth and colony formation suggesting that STAMP2 may have a role in cell proliferation. Taken together, these data suggest that STAMP2 may contribute to the normal biology of the prostate cell, as well as prostate cancer progression.

Edwards S, Campbell C, Flohr P, et al.
Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer.
Br J Cancer. 2005; 92(2):376-81 [PubMed] Free Access to Full Article Related Publications
In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types.

Porkka KP, Helenius MA, Visakorpi T
Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate.
Lab Invest. 2002; 82(11):1573-82 [PubMed] Related Publications
By using subtraction and cDNA array hybridizations, we recently identified an anonymous transcript that was differentially expressed in benign prostate hyperplasia and prostate cancer cell line PC-3. Here, we report the cloning of the full-length cDNA of the gene, designated STEAP2 (six-transmembrane epithelial antigen of the prostate 2). The gene is located at the chromosomal region 7q21 and encodes for a 490-amino acid protein with six predicted transmembrane domains and is predominantly expressed in prostate epithelial cells. Green fluorescent protein fusion construct indicated that the STEAP2 protein is localized mainly in the plasma membrane. Real-time quantitative RT-PCR showed that the gene is expressed at levels more than 10 times higher in normal prostate than in other tissues studied. Of the prostate cancer cell lines, STEAP2 was expressed in significant levels only in androgen-responsive LNCaP. The expression of STEAP2 was significantly higher (p = 0.002) in both untreated primary and hormone-refractory prostate carcinomas than in benign prostate hyperplasias, suggesting that it may be involved in the development of prostate cancer. As a cell-surface antigen, STEAP2 is a potential diagnostic or therapeutic target in prostate cancer.

Korkmaz KS, Elbi C, Korkmaz CG, et al.
Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.
J Biol Chem. 2002; 277(39):36689-96 [PubMed] Related Publications
We have identified a novel gene, six transmembrane protein of prostate 1 (STAMP1), which is largely specific to prostate for expression and is predicted to code for a 490-amino acid six transmembrane protein. Using a form of STAMP1 labeled with green fluorescent protein in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP1 is localized to the Golgi complex, predominantly to the trans-Golgi network, and to the plasma membrane. STAMP1 also localizes to vesicular tubular structures in the cytosol and colocalizes with the early endosome antigen 1 (EEA1), suggesting that it may be involved in the secretory/endocytic pathways. STAMP1 is highly expressed in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Furthermore, STAMP1 expression is significantly lower in the androgen-dependent human prostate xenograft CWR22 compared with the relapsed derivative CWR22R, suggesting that its expression may be deregulated during prostate cancer progression. Consistent with this notion, in situ analysis of human prostate cancer specimens indicated that STAMP1 is expressed exclusively in the epithelial cells of the prostate and its expression is significantly increased in prostate tumors compared with normal glands. Taken together, these data suggest that STAMP1 may have an important role in the normal prostate cell as well as in prostate cancer progression.

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

Cite this page: Cotterill SJ. STEAP2, Cancer Genetics Web: http://www.cancer-genetics.org/STEAP2.htm Accessed:

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: 15 March, 2017     Cancer Genetics Web, Established 1999