HGF/SF regulates expression of apoptotic genes in MCF-10A human mammary epithelial cells

Catherine Leroy, Julien Deheuninck, Sylvie Reveneau, Bénédicte Foveau, Zongling Ji, Céline Villenet, Sabine Quief, David Tulasne, Jean Pierre Kerckaert, Véronique Fafeur

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Hepatocyte growth factor/scatter factor (HGF/SF) induces scattering, morphogenesis, and survival of epithelial cells through activation of the MET tyrosine kinase receptor. HGF/SF and MET are involved in normal development and tumor progression of many tissues and organs, including the mammary gland. In order to find target genes of HGF/SF involved in its survival function, we used an oligonucleotide microarray representing 1,920 genes known to be involved in apoptosis, transcriptional regulation, and signal transduction. MCF-10A human mammary epithelial cells were grown in the absence of serum and treated or not with HGF/SF for 2 h. Total RNA was reverse-transcribed to cDNA in the presence of fluorescent Cy3-dUTP or Cy5-dUTP to generate fluorescently labeled cDNA probes. Microarrays were performed and the ratios of Cy5/Cy3 fluorescence were determined. The expression of three apoptotic genes was modified by HGF/SF, with A20 being upregulated, and DAXX and SMAC being downregulated. These changes of expression were confirmed by real-time quantitative PCR. According to current-knowledge, A20 is antiapoptotic and SMAC is proapoptotic, while a pro- or antiapoptotic function of DAXX is controversial. The fact that HGF/SF upregulates an antiapoptotic gene (A20) and downregulates a proapoptotic gene (SMAC) is in agreement with its survival effect in MCF-10A cells. This study identified novel apoptotic genes regulated by HGF/SF, which can contribute to its survival effect. © 2006 New York Academy of Sciences.
    Original languageEnglish
    Pages (from-to)188-202
    Number of pages14
    JournalAnnals of the New York Academy of Sciences
    Volume1090
    DOIs
    Publication statusPublished - Dec 2006

    Keywords

    • Apoptosis
    • Array
    • Breast
    • HGF/SF
    • MET
    • Target genes

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