title: Effects of mutant p53 genes on transformation of human mammary epithelial-cells.
abstract: MCF-10A cells are a spontaneously immortalized, nontransformed human mammary epithelial cell line that contains two normal p53 alleles and produces a normal p53 protein. We have recently shown that overexpression of several genes that are important for normal mammary gland development and for neoplastic transformation, such as transforming growth factor alpha, c-Ha-rns or c-erbB-2, leads to in vitro transformation of these cells (Ciardiello et al: Mol Carcinogen 6: 43-52, 1992). To investigate the neoplastic potential of mutated forms of the p53 gene on MCF-10A cells, we have constructed two expression vector plasmids containing two p53 mutants that were isolated from human primary breast carcinomas. Overexpression of either mutant p53 gene confers on MCF-10A cells the ability to grow in serum-free medium in monolayer culture and to form colonies in semi-solid medium. Furthermore, to determine whether a mutated p53 gene may cooperate with a point mutated c-Ha-ras and/or the normal c-erbB-2 protooncogenes in the transformation of these cells, we generated clones of MCF-10A cells that overexpress a combination of these gene pruducts. Although these cells were able to grow with a higher cloning efficiency in soft agar, none of the cell lines was tumorigenic when injected subcutaneously into immunodeficient mice.
authors.affiliation: UNIV NAPOLI FEDERICO II,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. UNIV PISA,FAC MED & CHIRURG,INST ANAT PATOL,I-56100 PISA,ITALY. FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. NCI,LTIB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892.
authors.forename: C
authors.initials: C
authors.lastname: Bianco
authors.forename: G
authors.initials: G
authors.lastname: Tortora
authors.forename: F
authors.initials: F
authors.lastname: Basolo
authors.forename: L
authors.initials: L
authors.lastname: Fiore
authors.forename: G
authors.initials: G
authors.lastname: Fontanini
authors.forename: G
authors.initials: G
authors.lastname: Merlo
authors.forename: D
authors.initials: D
authors.lastname: Salomon
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: F
authors.initials: F
authors.lastname: Ciardiello