We have previously shown that ovarian
tumors express prostate-derived
Ets transcription factor (PDEF). However, the precise role of PDEF in the prognosis of
ovarian cancer is unknown. In our study, we report for the first time that expression of PDEF in
tumor lesions of patients with
ovarian cancer is associated with favorable prognosis. Evaluation of samples from 40 patients with
ovarian cancer showed that early stage (IA) and borderline (IIB, III) ovarian
tumors expressed higher levels of PDEF
mRNA and
protein and lower levels of
survivin compared to late stage ovarian
tumors (IIIC and IV, p < 0.05). Normal ovarian tissues expressed the highest levels of PDEF
mRNA and
protein when compared to
tumor tissues (p < 0.05). A Log-Rank test showed that overall survival of patients with PDEF-positive and
survivin-negative ovarian
tumors was significantly longer than those with PDEF-negative and
survivin-positive
tumors (p < 0.01). Forced expression of PDEF in PDEF-negative ovarian
tumor cells inhibited
tumor cell growth, induced apoptosis, downregulated
survivin expression and its promoter activity. Furthermore, treatment of
ovarian cancer cells with
vitamin D or a
selenium compound resulted in re-expression of PDEF, downregulation of
survivin, induction of apoptosis and inhibition of
tumor cell growth when compared to untreated controls (p < 0.05). Together, these observations showed an inverse correlation between PDEF and
survivin expression and suggested that increased PDEF expression along with reduced
survivin was associated with prolonged survival of patients with
ovarian cancer.