Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene.
Mutations in the p53 gene are associated with a wide variety of human tumors, including those of the breast. To assess functionally the role of the p53 gene in the development of human breast cancer, we introduced either wild-type or mutant p53 cDNA into three human breast cancer cell lines by DNA transfection. The cell lines MDA-MB 468 and T47 D contain only single mutated copies of the p53 gene, whereas the status of p53 in the breast cancer cell line MCF 7 remains equivocal. Following transfection, MCF 7 cells continued to grow unaffected both in vitro and in vivo in the presence of high levels of expression of the exogenous wild-type p53 gene. In contrast, however, the continued expression of an exogenous wild-type p53 gene was incompatible with cellular growth in both the MDA-MB 468 and T47 D cell lines. Elevated levels of expression of the exogenous mutant p53 gene did not alter the growth of the cell lines in vitro. These data strongly suggest that the wild-type p53 gene can function as a suppressor of cellular growth in breast cancer cells. That the wild-type p53 gene does not suppress the growth of MCF 7 cells indicates that at least some human breast tumors can arise without functional inactivation of the p53 gene by mutation. These tumors may represent a separate prognostic group.
Department of Pediatrics, University of California, Irvine 92717.
G
G
Casey
M
M
Lo-Hsueh
M E
ME
Lopez
B
B
Vogelstein
E J
EJ
Stanbridge
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009355:Neomycin; D016133:Polymerase Chain Reaction; D014162:Transfection / Q000235:genetics*
D009355:Neomycin