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

Scientific Reports
Nikita A MitkinDmitry V Kuprash

Abstract

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 a...Continue Reading

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Citations

Mar 8, 2020·Journal of Cell Science·Julianna BlagihKaren H Vousden
Oct 1, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Anton LennikovHu Huang
Mar 15, 2018·Frontiers in Cellular and Infection Microbiology·Kirill V KorneevDmitry V Kuprash
Jul 30, 2019·Frontiers in Endocrinology·Marcelo G KazanietzMariana Cooke
Aug 28, 2015·Small·Seung Won ShinSoong Ho Um
Apr 27, 2019·Life Sciences·Muzammal HussainJinsong Liu
Apr 21, 2021·Seminars in Cell & Developmental Biology·Deepti SinghHifzur R Siddique
Aug 25, 2021·Journal of Cellular and Molecular Medicine·Chia-Chia ChaoJu-Fang Liu

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Methods Mentioned

BETA
transfection
immunoprecipitation
ChIP
PCR
FCS
Assay

Software Mentioned

Statistica
Excel

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