p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells
| Autor: | Marina A. Afanasyeva, Subir Biswas, Julia E. Kravchenko, Alisa M. Muratova, A. M. Schwartz, Nikita A. Mitkin, Arindam Bhattacharyya, Dmitry V. Kuprash, Dmitry V. Kochetkov, Christina D. Hook |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
CCR1
Receptors CXCR5 Transcriptional Activation CCR2 Breast Neoplasms C-C chemokine receptor type 6 CCR8 Biology Response Elements Article 03 medical and health sciences Chemokine receptor 0302 clinical medicine Humans CXCL14 Promoter Regions Genetic 030304 developmental biology 0303 health sciences Multidisciplinary Chemotaxis NF-kappa B Computational Biology Chemokine CXCL13 Gene Expression Regulation Neoplastic Enhancer Elements Genetic 030220 oncology & carcinogenesis Gene Knockdown Techniques Cancer research MCF-7 Cells XCL2 Female Tumor Suppressor Protein p53 CCL21 Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep09330 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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