NDLI: HPV-type-specific response of cervical cancer cells to cisplatin after silencing replication licensing factor MCM4

Content Provider	Springer Nature Link
Author	Das, Mitali Prasad, Shyam Babu Yadav, Suresh Singh Modi, Arusha Singh, Sunita Pradhan, Satyajit Narayan, Gopeshwar
Copyright Year	2015
Abstract	Minichoromosome maintenance (MCM) proteins play key role in cell cycle progression by licensing DNA replication only once per cell cycle. These proteins are found to be overexpressed in cervical cancer cells. In this study, we depleted MCM4, one of the MCM 2–7 complex components by RNA interference (RNAi) in four cervical cancer cell lines. The four cell lines were selected on the basis of their human papillomavirus (HPV) infection: HPV16-positive SiHa, HPV18-positive ME-180, HPV16- and HPV18-positive CaSki, and HPV-negative C-33A. The MCM4-deficient cells irrespective of their HPV status grow for several generations and maintain regular cell cycle. We did not find any evidence of augmented response to a short-term (48 h) cisplatin treatment in these MCM4-deficient cells. However, MCM4−/HPV16+ SiHa cells cannot withstand a prolonged treatment (up to 5 days) of even a sublethal dosage of cisplatin. They show increased chromosomal instability compared to their control counterparts. On the other hand, MCM4-deficient CaSki cells (both HPV16+ and 18+) remain resistant to a prolonged exposure to cisplatin. Our study indicates that cervical cancer cells may be using excess MCMs as a backup for replicative stress; however, its regulatory mechanism is dependent on the HPV status of the cells.
Starting Page	9987
Ending Page	9994
Page Count	8
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	36
Issue Number	12
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-07-19
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Cervical cancer HPV status MCM4 RNA interference Cisplatin Chromosomal instability Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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