PTEN-negative endometrial cancer cells protect their genome through enhanced DDB2 expression associated with augmented nucleotide excision repair
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Published:2023-05-04
Issue:1
Volume:23
Page:
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ISSN:1471-2407
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Container-title:BMC Cancer
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language:en
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Short-container-title:BMC Cancer
Author:
Hameed J S Fathima,Devarajan Anjali,M S Devu Priya,Bhattacharyya Ahel,Shirude Mayur Balkrishna,Dutta Debasree,Karmakar Parimal,Mukherjee Ananda
Abstract
AbstractBackgroundEndometrial cancer (EC) arises from uterine endometrium tissue and is the most prevalent cancer of the female reproductive tract in developed countries. It has been predicted that the global prevalence of EC will increase in part because of its positive association with economic growth and lifestyle. The majority of EC presented with endometrioid histology and mutations in the tumor suppressor gene PTEN, resulting in its loss of function. PTEN negatively regulates the PI3K/Akt/mTOR axis of cell proliferation and thus serves as a tumorigenesis gatekeeper. Through its chromatin functions, PTEN is also implicated in genome maintenance procedures. However, our comprehension of how DNA repair occurs in the absence of PTEN function in EC is inadequate.MethodsWe utilized The Cancer Genome Atlas (TCGA) data analysis to establish a correlation between PTEN and DNA damage response genes in EC, followed by a series of cellular and biochemical assays to elucidate a molecular mechanism utilizing the AN3CA cell line model for EC.ResultsThe TCGA analyses demonstrated an inverse correlation between the expression of the damage sensor protein of nucleotide excision repair (NER), DDB2, and PTEN in EC. The transcriptional activation of DDB2 is mediated by the recruitment of active RNA polymerase II to the DDB2 promoter in the PTEN-null EC cells, revealing a correlation between increased DDB2 expression and augmented NER activity in the absence of PTEN.ConclusionOur study indicated a causal relationship between NER and EC that may be exploited in disease management.
Funder
Council of Scientific and Industrial Research, India
University Grants Commission
Science and Engineering Research Board
Department of Biotechnology, Ministry of Science and Technology, India
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
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