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Srivastava P , Russo J , Mgbonyebi OP , Russo IH
Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells
Anticancer Research. 1998 Nov-Dec;18(6A) :4003-4010
PMID: ISI:000078056000006   
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The glycoprotein hormone, human chorionic gonadotropin (hCG) inhibits mammary tumorigenesis through induction of differentiation, and inhibits the proliferation of human breast epithelial cells (HBEC) in vitro. The present study was designed to determine whether the inhibitory effects of hCG was associated with the modulation of apoptotic gene expression. MCF-10F, a normal immortalized HBEC, BP1-E, benzo(a)pyrene (BP) transformed cell line and the urothelial cell line T24, were treated with 100 IU/ml of a commercially available preparation of hCG. Cell growth analysis and RNA extraction for determination of apoptotic gene expression were performed at 24 and 120 hrs of hCG treatment. Both hCG-treated and control cells grew at similar rates for, the first 24 hours. A significant reduction in the number of viable MCF-10F and BP1-E cells occurred by 120 hours of treatment, whereas the number of both hCG treated and control T24 cells were similar Northern blot analysis revealed that the 24 hour-hCG treatment induced an elevation in the expression of the apoptotic genes TRPM2, ICE, TGF-beta, p53, bax, and p21(WAF1/CIP1) in MCF-10F cells. By 120 hours of treatment MCF-10F cells maintained the same level of gene expression observed at 24 hours, except for a reduction in c-myc and bax. Control cells exhibited an elevation the expression of TRPM2 in the TGF-beta p53, bax, and p21(WAF1/CIP1), whose levels became similar to those observed in hCG-treated cells. The 24 hour-treated BP1-E cells showed activation of ICE, bax and p21(WAF1/CIP1). However, TRPM2 expression was moderately activated By 120 hours TRPM2, ICE, TGF-beta, c-myc and p21(WAF1/CIP1) were elevated in both treated and control cells except bax which was slightly down- regulated the levels of bc12 were significantly decreased by hCG treatment. Gene expression was not modifed by hCG treatment in T24 cells. Our findings suggest that hCG induced an acceleration in the expression of apoptotic genes, which became evident before detection of cell growth inhibition. Gene activation differed among immortalized, and chemically transformed cells, suggesting that hCG might utilize both p53 dependent and p53 independent pathways for inhibiting cell cycle progression. The importance of these findings lies in the potential rise of agents like hCG for the chemoprevention and chemotherapy of breast cancer.
Times Cited: 9 English Article 157HR ANTICANCER RES