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p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cellsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 22 ноября 2015 г.
- Авторы: Mitkin N.A., Hook C.D., Schwartz A.M., Biswas S., Kochetkov D.V., Muratova A.M., Afanasyeva M.A., Kravchenko J.E., Bhattacharyya A., Kuprash D.V.
- Журнал: Scientific reports
- Том: 5
- Год издания: 2015
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 9330
- DOI: 10.1038/srep09330
- Аннотация: Elevated expression of chemokine receptors in tumors has been reported in many instances and is related to a number of survival advantages for tumor cells including abnormal activation of prosurvival intracellular pathways. In this work we demonstrated an inverse correlation between expression levels of p53 tumor suppressor and CXCR5 chemokine receptor in MCF-7 human breast cancer cell line. Lentiviral transduction of MCF-7 cells with p53 shRNA led to elevated CXCR5 at both mRNA and protein levels. Functional activity of CXCR5 in p53-knockdown MCF-7 cells was also increased as shown by activation of target gene expression and chemotaxis in response to B-lymphocyte chemoattractant CXCL13. Using deletion analysis and site-directed mutagenesis of the cxcr5 gene promoter and enhancer elements, we demonstrated that p53 appears to act upon cxcr5 promoter indirectly, by repressing the activity of NFκB transcription factors. Using chromatin immunoprecipitation and reporter gene analysis, we further demonstrated that p65/RelA was able to bind the cxcr5 promoter in p53-dependent manner and to directly transactivate it when overexpressed. Through the described mechanism, elevated CXCR5 expression may contribute to abnormal cell survival and migration in breast tumors that lack functional p53.
- Добавил в систему: Купраш Дмитрий Владимирович