title: Characterization of human breast cancer cell lines for the studies on p53 in chemical carcinogenesis.
abstract: To know whether the molecular responses to chemical carcinogens reflect only cell line specific molecular responses, or whether they can be regarded as characteristic of breast tissue, we have characterized four human breast cancer cell lines (MDA-MB-231, MDA-MB-468, T47-D, ZR-75-1). The activation of benzo(a)pyrene (BP), a model compound of polycyclic aromatic hydrocarbons, to its genotoxic BP-diolepoxide (BPDE) and p53 response and cell viability after BP exposure, and the p53 status in these cell lines were analyzed. Both TP53 (exons 5-8) mutations and total and phospho-p53 were analyzed. Three of the four cell lines clearly activated BP to BPDE-DNA adducts (MDA-MB-468, T47-D, ZR-75-1) and three had a mutation in the TP53 gene (MDA-MB-231, MDA-MB-468, T47-D). After BP-treatment the strongest p53 protein induction and phosphorylation at serine 392 was found in ZR-75-1 cells with a wt TP53 gene. Viability decreased dramatically only in ZR-75-1 and MDA-MB-468 cells although the relative cell number was reduced in all the cell lines suggesting that BP affects cell proliferation. In conclusion, a TP53 mutation does not necessarily lead to a loss of p53 protein response. This study stresses the importance of characterization of all human cancer cell lines for the intended targets of study.
authors: School of Pharmacy Toxicology, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627 (Yliopistonranta 1 C), FI-70211 Kuopio, Finland. Marjo.Huovinen@uef.fi
authors: Marjo
authors: M
authors: Huovinen
authors: Jarkko
authors: J
authors: Loikkanen
authors: Päivi
authors: P
authors: Myllynen
authors: Kirsi H
authors: KH
authors: Vähäkangas
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide