title: p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells.
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 and migration in breast tumors that lack functional p53.
authors: Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Nikita A
authors: NA
authors: Mitkin
authors: Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Christina D
authors: CD
authors: Hook
authors: Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Anton M
authors: AM
authors: Schwartz
authors: Department of Zoology, University of Calcutta, Ballygunge Circular Road 35, 700019 Calcutta, India.
authors: Subir
authors: S
authors: Biswas
authors: Group of Regulation of Genome Transcription, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Dmitry V
authors: DV
authors: Kochetkov
authors: 1] Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia [2] Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Leninskye gory 1, 119234 Moscow, Russia.
authors: Alisa M
authors: AM
authors: Muratova
authors: Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Marina A
authors: MA
authors: Afanasyeva
authors: Group of Regulation of Genome Transcription, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia.
authors: Julia E
authors: JE
authors: Kravchenko
authors: Department of Zoology, University of Calcutta, Ballygunge Circular Road 35, 700019 Calcutta, India.
authors: Arindam
authors: A
authors: Bhattacharyya
authors: 1] Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, 119991 Moscow, Russia [2] Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Leninskye gory 1, 119234 Moscow, Russia.
authors: Dmitry V
authors: DV
authors: Kuprash
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D019295:Computational Biology; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054380:Receptors, CXCR5 / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054382:Chemokine CXCL13; D016328:NF-kappa B; D054380:Receptors, CXCR5; D016159:Tumor Suppressor Protein p53