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PMS2 expression in epithelial ovarian cancer is posttranslationally regulated by Akt and essential for

Jinghui Jia1,2, Zehua Wang2, Jing Cai2

  • 1Department of Obstetrics and Gynecology, Air Force General Hospital, PLA, Beijing, 100142, People's Republic of China.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|October 2, 2015
PubMed

Insights

Deficiency in PMS2, a DNA repair protein, is common in ovarian cancer and linked to cisplatin resistance. Akt activation degrades PMS2, hindering apoptosis and chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Epithelial ovarian cancer (EOC) is a leading cause of cancer death, often diagnosed at advanced stages.
  • Cisplatin resistance significantly limits treatment efficacy in EOC.
  • DNA mismatch repair (MMR) pathway defects can influence chemoresistance, but the role of PMS2 in this process is unclear.

Purpose of the Study:

  • To investigate the role of postmeiotic segregation increased 2 (PMS2) in cisplatin resistance in epithelial ovarian cancer.
  • To elucidate the molecular mechanisms by which PMS2 influences chemoresistance.

Main Methods:

  • Analysis of PMS2 expression and Akt phosphorylation in EOC cell lines and tissues.
  • Co-immunoprecipitation (co-IP) assays to assess protein interactions.
  • Protein stability assays to evaluate PMS2 degradation.
  • Functional experiments assessing apoptosis and cell cycle arrest.

Main Results:

  • Frequent deficiency of PMS2 and increased Akt phosphorylation were observed in EOC.
  • Activated Akt directly binds to and promotes the degradation of PMS2 in EOC cells.
  • PMS2 is essential for cisplatin-induced apoptosis and G2/M cell cycle arrest.

Conclusions:

  • Activated Akt-mediated degradation of PMS2 contributes to cisplatin resistance in EOC.
  • Targeting PMS2 stabilization could be a therapeutic strategy to enhance cisplatin sensitivity in ovarian cancer.
Keywords:
AktCisplatin resistantEOCEpithelial ovarian cancerMMRMismatch repairPMS2Postmeiotic segregation increased 2Protein kinase B

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