p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells

Nikita A. Mitkin; Christina D. Hook; Anton M. Schwartz; Subir Biswas; Dmitry V. Kochetkov; Alisa M. Muratova; Marina A. Afanasyeva; Julia E. Kravchenko; Arindam Bhattacharyya; Dmitry V. Kuprash

doi:10.1038/srep09330

journal article Open Access Mar 19, 2015

p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells

Nikita A. Mitkin

Christina D. Hook Anton M. Schwartz Subir Biswas

Dmitry V. Kochetkov Alisa M. Muratova Marina A. Afanasyeva Julia E. Kravchenko Arindam Bhattacharyya

Dmitry V. Kuprash

Scientific Reports Vol. 5 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep09330

Abstract

AbstractElevated 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.

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References

Details

Published: Mar 19, 2015
Vol/Issue: 5(1)
License: View

Authors

Arindam Bhattacharyya

Department of Zoology, University of Calcutta, Kolkata, West Bengal 700019, India

D

Dmitry V. Kuprash

Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; Biological Faculty, Lomonosov Moscow State University, 119234 Moscow, Russia

Cite This Article

Nikita A. Mitkin, Christina D. Hook, Anton M. Schwartz, et al. (2015). p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells. Scientific Reports, 5(1). https://doi.org/10.1038/srep09330

p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells

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