A role for STEAP2 in prostate cancer progression

Abstract

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.

Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients

“…STEAP2 (Seven Transmembrane Epithelial Antigen of the Prostate 2) is a gene primarily expressed in the prostate and the ovary is the only other area with a significant expression [36]. e roles of STEAP2 in OvCa may be similar to prostate cancer in which STEAP2 was observed to be upregulated and associated with advanced stage and Gleason score [37,38]. e overexpression of STEAP2 induced the normal prostate cells to gain an ability to migrate and invade [36] while the knockdown of STEAP2 significantly reduced proliferation and migration of prostate cancer cells [39].…”

Enduring epigenetic landmarks define the cancer microenvironment

“…Notably, the tsDMRs are strongly overrepresented in developmental gene families and genes involved in endocrine hormone secretion, such as TBX3 (Holterhus et al 2007;Beukers et al 2015), suggesting that they are associated with functional roles in cancer progression. Indeed specific tsDMRs were found in known tumor suppressor genes (for example, EHF [Albino et al 2012] and MCC [KohonenCorish et al 2007]) and oncogenes (for example, STEAP2 [Whiteland et al 2014]). Collectively, the tsDMRs suggest a convergent malignant epigenetic pathway across cell types.…”

Six‐Transmembrane Epithelial Antigen of the Prostate‐1 (STEAP‐1)–Targeted Ultrasound Imaging Microbubble Improves Detection of Prostate Cancer In Vivo

“…The level of STEAP‐1 expression in LNCaP cell is higher than that in PC3 cells; thus, the LNCaP xenograft model and PC3 xenograft model were created, respectively, to confirm the conjugation of STEAP‐1–targeted SonoVue microbubbles and tumors in vivo. We found that the amount of improvement of PI and AUC by STEAP‐1–targeted SonoVue microbubbles in LNCaP xenograft models were significantly higher than those in the PC3 xenograft models, which are in agreement with the levels of STEAP‐1 expression in these cell lines.…”