Cloning and Characterization of a Novel Six-Transmembrane Protein STEAP2, Expressed in Normal and Malignant Prostate

Abstract

SUMMARY: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 ϭ 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. (Lab Invest 2002, 82:1573-1582.

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

“…STEAP2, which includes ARBS no. 4 in intron 3, has been originally cloned as a STEAP homolog gene that encodes a transmembrane protein expressed in prostate cancer (Porkka et al, 2002). Although androgen responsiveness of STEAP2 was not reported previously, our data showed that it was a novel androgen target gene with a genuine ARBS in intron 3, which was also associated with histone acetylation.…”

Androgen signaling and its interactions with other signaling pathways in prostate cancer

“…(27) STAMP1 is highly restricted to prostate for expression and is overexpressed in prostate cancer compared with benign prostate tissue. (28,29) STAMP1 expression is correlated with the presence of functional AR, even though it appears not to be androgen regulated. (28) STAMP2 has a more general tissue distribution.…”

STEAP Proteins: From Structure to Applications in Cancer Therapy

“…Human tissues express 4 different mRNA transcripts, 3 of them resulting from alternative splicing of the last exon, with estimated sizes of 2.2, 4.0, 4.5, and 6.5 kb (7). However, there is some controversy about the size of the larger transcript, which has also been identified as having 7.5 kb (8). No significant rearrangements of the gene have been detected in LNCaP, PC3, and DU145 prostate cancer cell lines, but 4 sites of base variations were identified in prostate cancer cell lines and in normal prostate tissue.…”

“…These cDNA variations originate from a neutral substitution from CTC to CTT with no amino acid change at codon 272 and 3 missense substitutions: TTT to TGT, leading to Phe17Cys; CGA to CAA, leading to Arg456Gln; and ATG to ATT, resulting in Met475Ile. The open reading frame of the STEAP2 gene is located within the third exon and gives rise to a 490-amino acid protein with a predicted molecular weight of 56 kilodaltons (7,8).…”