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Fibulin-1 interacts with Sex Hormone Binding Globulin and is linked to less aggressive estrogen-dependent breast cancers.
Marano, Francesca; Zunino, Valentina; Frairia, Roberto; Arvat, Emanuela; Castellano, Isabella; Bosco, Ornella; Catalano, Maria Graziella; Fortunati, Nicoletta.
Afiliação
  • Marano F; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Zunino V; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Frairia R; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Arvat E; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy; Division of Oncological Endocrinology, Città della Salute e della Scienza University Hospital, Corso Bramante 88, I-10126 Turin, Italy.
  • Castellano I; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Bosco O; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Catalano MG; Department of Medical Sciences, University of Turin, Via Genova 3, I-10126 Turin, Italy.
  • Fortunati N; Division of Oncological Endocrinology, Città della Salute e della Scienza University Hospital, Corso Bramante 88, I-10126 Turin, Italy. Electronic address: nfortunati@cittadellasalute.to.it.
Life Sci ; 207: 372-380, 2018 Aug 15.
Article em En | MEDLINE | ID: mdl-29940241
AIMS: Interaction of Sex Hormone-Binding Globulin (SHBG) with estrogen-sensitive breast cancer cells has a protective role against estrogen exposure. No specific membrane receptor for SHBG had been identified by now, but a putative interaction of SHBG with extracellular matrix associated-proteins (e.g. fibulins) was suggested. In this study we investigated the expression of fibulins, their functional relationship with SHBG and involvement in behavior of estrogen-sensitive breast cancer. MAIN METHODS: Gene expression of fibulins was performed by Real time-PCR on two estrogen-sensitive breast cancer cell lines, MCF-7 and T47D. Fibulin-1 protein expression and localization were determined by Western blot and immunofluorescence. SHBG interaction with-fibulin-1 was assessed by GST-pull down assay. MCF-7 cell growth and gene expression, after fibulin-1 silencing by siRNA, were evaluated. Finally, the expression of fibulin-1 was correlated to clinical and pathological data of 21 breast cancer tissue samples. KEY FINDINGS: Fibulin-1 was expressed in both cell lines and it was increased by estradiol. SHBG interacted with fibulin-1C; proteins co-localized at MCF-7 cell membranes and SHBG localization at membranes disappeared after silencing fibulin-1. Fibulin-1 silencing, moreover, generated MCF-7 cells unresponsive to estradiol and SHBG and characterized by increased proliferation. Finally, in breast cancer tissue samples expressing fibulin-1 the proliferation index was significantly lower than in fibulin-1 negative samples. SIGNIFICANCE: Fibulin-1 interacts with SHBG, it is associated with a less aggressive behavior of breast cancer cells and correlates to a better prognosis of the tumor.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Ligação ao Cálcio / Globulina de Ligação a Hormônio Sexual Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Ligação ao Cálcio / Globulina de Ligação a Hormônio Sexual Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article