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Steroidogenesis-inducing protein: An enigmatic protein with multiple biological functions

2008-10-09 , Khan, Shafiq A.

SIP was isolated and characterized from human ovarian follicular fluid in our laboratory on the basis of its profound effects on steroid production in testicular, ovarian and adrenal cells. Later studies showed that SIP is also a potent mitogen and stimulated DNA synthesis in testicular Leydig cells, ovarian granulosa cells and in cell lines derived from ovarian epithelial carcinomas. Partial amino acid sequence analysis of this protein revealed that SIP is a novel protein which shows similarities with immunoglobulins and with a recently characterized DING family of proteins. Antibodies raised against specific SIP peptide blocked the activity of SIP on DNA synthesis and on steroid production in testicular cells. Using these antibodies we also determined the expression of SIP in different tissues and cell lines including prostate cancer cells. A SIP protein was detected in the rat testes, ovarian granulosa cells, ovarian epithelial cancer cell lines and in several prostate cancer cell lines. Furthermore, treatment with purified SIP resulted in induction of proliferation of prostate cancer cells similar to that seen in ovarian cancer cells and in other cell types. Based on these studies we hypothesize that SIP is produced by prostate cancer cells in the advanced stages of disease and serves as an autocrine regulator of cell proliferation in these cells. Furthermore, we hypothesize that SIP may exert its steroidogenic effects on these cells resulting in synthesis of steroids which may serve as ligands for AR and hence may lead to insensitivity to exogenous androgens