Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients.
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.
Ghadersohi
Ali
A
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. ali.ghadersohi@roswellpark.org
Odunsi
Kunle
K
Zhang
Shaozeng
S
Azrak
Rami G
RG
Bundy
Brian N
BN
Manjili
Masoud H
MH
Li
Fengzhi
F
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D053208:Kaplan-Meier Estimate; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C403974:SPDEF protein, human; D000077022:Survivin