Changes in follistatin levels by BRCA1 may serve as a regulator of ovarian carcinogenesis

Follistatin is a folliculogenesis regulating protein that has been found in relatively high concentration in the female ovarian tissues. Follistatin acts as an antagonist to the function of Activin, which is often found elevated in ovarian carcinogenesis and thus presents a possibility for therapeutic intervention in controlling ovarian cancer. Most of the ovarian cancer occurs in its ovarian surface epithelium (OSE) cells. Although breast cancer susceptibility gene 1 (BRCA1) is a known tumor suppressor for breast cancer but its role in ovarian cancer is beginning to unfold. We have shown that in ovarian carcinoma cells (SKOV3), stable overexpression of BRCA1 stimulates Follistatin secretion and simultaneously downregulates Activin expression. Moreover, knock down of BRCA1 in immortalized OSE (IOSE) cells from human ovarian tissue demonstrates downregulation of Follistatin secretion with simultaneous up regulation of Activin expression. IOSE cells generated from an ovarian cancer patient with BRCA1 mutation failed to secrete Follistatin in the medium. Our results indicate a novel function for BRCA1 in the form of regulation of the expression of Follistatin in the ovarian cells.

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Karve TM, Preet A, Sneed R, Salamanca C, Li X, Xu J, Kumar D, Rosen EM, Saha T