High MDC1 expression in cervical cancer cells can affect the chemo- and radiotherapeutic response as its depletion leads to increased cell death

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dc.contributor.author Singh, Neeru
dc.contributor.author Bhakuni, Rashmi
dc.contributor.author Kirubakaran, Sivapriya
dc.date.accessioned 2019-06-25T11:45:21Z
dc.date.available 2019-06-25T11:45:21Z
dc.date.issued 2018-07
dc.identifier.citation Singh, Neeru; Bhakuni, Rashmi and Kirubakaran, Sivapriya, "High MDC1 expression in cervical cancer cells can affect the chemo- and radiotherapeutic response as its depletion leads to increased cell death", Cancer Research, DOI: 10.1158/1538-7445.AM2018-772, vol. 78, no. 13 Supplement, pp. 772-772, Jul. 2019 (Abstract). en_US
dc.identifier.issn 0008-5472
dc.identifier.issn 1538-7445
dc.identifier.uri https://doi.org/10.1158/1538-7445.AM2018-772
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/4564
dc.description.abstract Cervical cancer is the third most frequent cancer and common cause of death in women worldwide. The work presented identifies mediator of DNA damage checkpoint 1 (MDC1) as an important molecular target to increase sensitivity of cervical cancer cells to chemo or radiotherapy. MDC1 functions as an adaptor protein for recruitment and retention of many other DNA damage repair proteins in ataxia telangiectasia mutated (ATM) pathway for double-stranded DNA damage repair. It is reported to be highly expressed in cervical cancer cells. Also, its expression tends to increase with increase in malignancy. We have studied in detail MDC1 mRNA expression in three cervical cancer cell lines, HeLa, SiHa and CasKi, in response to various genotoxic stresses including some known inhibitors, UV exposure or gamma irradiation through quantitative PCR. The cellular response to the DNA damage resulted in increase in MDC1 expression, which declined with increase in treatment time period. Protein expression and activation by Western blotting with anti-MDC1 and anti-phosphoMDC1 antibody indicated a higher level of phosphorylated as compared to unphosphorylated MDC1. The significance of this increase in MDC1 expression was studied by generating stable cell lines knocked down for MDC1 expression. The modified cell lines were assessed for apoptosis through various assays, including flow cytometry, and showed greater cell death in response to DNA damage. In summary, high MDC1 expression can significantly affect chemo or radiotherapeutic response and its inhibition can improve sensitivity to these treatments.
dc.description.statementofresponsibility by Neeru Singh, Rashmi Bhakuni and Sivapriya Kirubakaran
dc.format.extent vol. 78, no. 13 Supplement, pp. 772-772
dc.language.iso en en_US
dc.publisher AACR en_US
dc.title High MDC1 expression in cervical cancer cells can affect the chemo- and radiotherapeutic response as its depletion leads to increased cell death en_US
dc.type Article en_US
dc.relation.journal Cancer Research


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