Prostate‐derived Ets transcription factor (PDEF) is a potential prognostic marker in patients with prostate cancer

Abstract

Background Reduced expression of prostate-derived Ets transcription factor (PDEF) leads to morphologic change as well as increased migration and invasiveness of prostate cancer cells. However, the clinical relevance of PDEF expression and its relationship to anti-apoptotic protein survivin is yet to be determined. Methods Tissue microarrays of 73 prostate carcinomas and their adjacent benign prostate tissue, as well as 50 benign prostates were evaluated for PDEF expression by immunohistochemistry. Results were confirmed in available tumor tissues using Western blot and RT-PCR. Expression of survivin in prostate carcinoma and benign tissues were determined using Western blot. Results and correlation with clinical data were statistically analyzed. Results Patients’ specimens with low Gleason scores (GS<5) expressed higher levels of PDEF protein and lower levels of survivin protein when compared with moderate to high Gleason scores tumors (GS >6). Patients with PDEF-positive tumor survived significantly longer (p<0.0001) than patients with PDEF-negative tumor, and the 8-year survival rate was 94% and 40%, respectively. PDEF expression was detected at the highest levels in benign tissues and was down-regulated or lost in 30 recently diagnosed prostate carcinomas. Re-expression of PDEF in prostate cancer cells inhibited survivin expression. Treatment of prostate cancer cells with methylseleninic acid resulted in restoration of PDEF expression, down-regulation of survivin and inhibition of tumor cell growth when compared with untreated controls (p< 0.05). Conclusions These studies demonstrated an inverse correlation between PDEF and survivin expression, and that up-regulation of PDEF was associated with a favorable prognosis in patients with clinically localized prostate cancer.

The Transcription Factor Sterile Alpha Motif (SAM) Pointed Domain-containing ETS Transcription Factor (SPDEF) Is Required for E-cadherin Expression in Prostate Cancer Cells

“…We also demonstrated that there is an inverse relationship between SPDEF expression and MMP9 expression in the clinical samples in tissue microarray having both normal and cancerous tumor samples of prostate cancer (10). Our results demonstrat-ing the loss of SPDEF and aggressive prostate cancer have been confirmed by at least two other independent studies (11,12); one follow-up study in fact suggests that loss of SPDEF could be a predictor not only of aggressive prostate cancer but also of prostate cancer-associated death (12). Taken together, these studies clearly provide compelling evidence of the association between loss of SPDEF and aggressive prostate cancer.…”

The Transcription Factor SPDEF Suppresses Prostate Tumor Metastasis

“…Our findings, that SPDEF expression limits the ability of prostate tumor cells to survive in the circulation and thereby establish metastases, are concordant with studies showing that SPDEF protein expression is decreased or undetectable in a majority of advanced/metastatic human prostate tumors (12,14), suggesting that the loss of SPDEF may in part contribute to prostate tumor metastasis, at least in subsets of patients. This would explain the positive correlation between the loss of SPDEF expression in clinical specimens of prostate cancer and cancer specific death in these patients, as observed recently (15). Our exciting results suggest that SPDEF may represent a modifiable therapeutic target to prevent or decrease tumor cell survival or growth at secondary sites in prostate cancer and perhaps other malignancies.…”

“…These studies also suggested that SPDEF expression suppressed an aggressive phenotype in prostate cancer. Our findings are in contrast to a report by Sood et al (13) but have been confirmed and even extended by two additional groups (14,15). In fact, Ghadersohi et al (15) associated SPDEF expression with a favorable prognosis in localized prostate cancer.…”

“…Our findings are in contrast to a report by Sood et al (13) but have been confirmed and even extended by two additional groups (14,15). In fact, Ghadersohi et al (15) associated SPDEF expression with a favorable prognosis in localized prostate cancer. Taken together, based on these limited studies, the loss of SPDEF appears to be an indicator of aggressive prostate cancer.…”

SPDEF Inhibits Prostate Carcinogenesis by Disrupting a Positive Feedback Loop in Regulation of the Foxm1 Oncogene

“…In advanced prostate cancer and prostate cancer-derived cell lines, SPDEF was either decreased or lost [23], [34]. It was also shown that SPDEF expression is decreased during the transition from low-grade to high-grade prostate cancer [23], [34], [35]. Two studies had shown correlation between decreased expression of SPDEF and poor prognosis in prostate cancer [23], [35].…”