|Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells.|
|PMID: 9891438 Owner: NLM Status: MEDLINE|
|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, a 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 p21WAF1/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 in the expression of TRPM2, TGF-beta, p53, bax, and p21WAF1/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 p21WAF1/CIP1. However, TRPM2 expression was moderately activated. By 120 hours TRPM2, ICE, TGF-beta, c-myc and p21WAF1/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 modified 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 use of agents like hCG for the chemoprevention and chemotherapy of breast cancer.|
|P Srivastava; J Russo; O P Mgbonyebi; I H Russo|
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|Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.|
|Title: Anticancer research Volume: 18 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 1998 Nov-Dec|
|Created Date: 1999-02-11 Completed Date: 1999-02-11 Revised Date: 2008-11-21|
Medline Journal Info:
|Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: GREECE|
|Languages: eng Pagination: 4003-10 Citation Subset: IM|
|Breast Cancer Research Laboratory, Fox Chase Cancer Center Philadelphia, PA 19111, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Benzo(a)pyrene / pharmacology
Breast / cytology, drug effects*, metabolism
Cell Division / drug effects
Cell Line, Transformed
Chorionic Gonadotropin / pharmacology*, physiology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics
Epithelial Cells / cytology, drug effects*, metabolism
Gene Expression Regulation / drug effects, physiology*
Genes, Tumor Suppressor
Glycoproteins / genetics
Neoplasm Proteins / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2*
Proto-Oncogene Proteins c-myc / genetics
Receptors, LH / physiology
Transforming Growth Factor beta / genetics
Urothelium / cytology, drug effects, metabolism
bcl-2-Associated X Protein
|CA64896/CA/NCI NIH HHS|
|0/BAX protein, human; 0/CDKN1A protein, human; 0/CLU protein, human; 0/Chorionic Gonadotropin; 0/Clusterin; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Glycoproteins; 0/Molecular Chaperones; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/Receptors, LH; 0/Transforming Growth Factor beta; 0/bcl-2-Associated X Protein; 50-32-8/Benzo(a)pyrene|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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