The Essential Role of PAX8 in Endometrial Cancer

Introduction:

Endometrial carcinoma (EC), cancer of the lining of the uterus, is the most common gynecological cancer and the fourth-most common cancer in women worldwide. EC subtypes include endometrioid adenocarcinoma being the most frequent type, uterine papillary serous carcinoma (UPSC), uterine clear-cell carcinoma, and several other rare forms. UPSC, a prototypical Type II EC, is histologically and molecularly similar to high-grade ovarian cancer. It is characterized by p53 mutations and copy number variations. PAX8 is an essential transcription factor during embryonic development of the Müllerian duct, which is the precursor of the epithelial lining of female reproductive organs, and it is expressed in nearly 100% of USPCs.

Material and method:

To test whether PAX8 is essential for proliferation of EC, we knocked down (KD) PAX8 using RNA interference and shRNA. PAX8 KD was confirmed using western blot analysis and immunofluorescent staining, and EC cell viability was measured using XTT assay. The effect of PAX8 KD on cell cycle progression was measured using FACS analysis and TUNEL assays and western blot for cleaved PARP were used to study apoptosis.

Results and discussion:

PAX8 silencing in EC cells decreased cell viability; we show that this effect was due to apoptosis of cancer cells. We show that similar to our previous finding in ovarian cancer, in USPC PAX8 regulates a mutant GOF p53, and this effect can mediate its pro-proliferative effect.

Conclusion:

We show here for the first time that PAX8 plays an essential anti-apoptotic role in USPC.

*Key words: Uterine serous papillary carcinoma, endometrial cancer, PAX8.