Fibulin-1 interacts with Sex Hormone Binding Globulin and is linked to less aggressive estrogen-dependent breast cancers

In this study we investigated the expression of fibulins, their functional relationship with SHBG and involvement in behavior of estrogen-sensitive breast cancer.Main methodsGene 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 findingsFibulin-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.SignificanceFibulin-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.
Source: Life Sciences - Category: Biology Source Type: research

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