title: Regulation of CXCR4 gene expression in breast cancer cells under diverse             stress conditions.
abstract: Chronic inflammation is a critical component in breast cancer progression.             Pro-inflammatory mediators along with growth/survival factors within the tumor             microenvironment potentiate the expression of pro-inflammatory cytokines (IL-1,             IL-6, TNF-α), chemotactic cytokines and their receptors (CXCR4, CXCL12, CXCL8)             and angiogenic factors (VEGF) that often overcome the effect of anti-inflammatory             molecules (IL-4, IL-10) thus evading the host's antitumor immunity. Detailed knowledge,             therefore, of the regulatory mechanisms determining cytokine levels is essential             to understand the pathogenesis of breast cancer. HIF-1α and NF-κB transcription             factors are important players for the establishment of a pro-inflammatory and             potentially oncogenic environment. HIF-1α is the key mediator of the cellular             response to oxygen deprivation and induces the expression of genes involved in             survival and angiogenesis within solid hypoxic tumors. The expression of these             genes is often modulated by the p53 tumor suppressor protein that induces apoptosis             or cell cycle arrest in neoplastic cells. Functional crosstalk between HIF-1α             and p53 pathways mediated by modulators shared between the two transcription factors             such as SRC-1 and SIRT-1 differentially regulate the expression of distinct subsets             of their target genes under variable stress conditions. In an attempt to shed             light on the complex regulatory mechanisms involved in cancer-related inflammation,             we investigated the role of the two common p53 and HIF-1α co-regulators SRC-1             and SIRT-1, in the expression of the highly potent metastatic chemokine receptor             CXCR4. Both SRC-1 and SIRT-1 overexpression in DSFX-treated MCF-7 cells reduced             CXCR4 cellular levels implying that both co-regulators are crucial factors in             the determination of the metastatic potential of breast cancer cells.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Stopford Building,                     University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Andreou
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Rajendran
authors.forename: Marija
authors.initials: M
authors.lastname: Krstic-Demonacos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Demonacos
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D061986:MCF-7 Cells; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005047:Etoposide; D056920:Nuclear Receptor Coactivator 1; D056564:Sirtuin 1