WILD-TYPE P53 SUPPRESSES THE MALIGNANT PHENOTYPE IN BREAST-CANCER CELLS CONTAINING MUTANT P53 ALLELES

We have examined the effect of expression of a retrovirally mediated wild-type (wt) p53 allele on the neoplastic properties of five human breast cancer cell lines expressing mutant p53. After infection with the retroviral vector Lhp53RNL expressing both the neomycin phosphotransferase gene and the wt p53 gene, the ability of infected cells to form colonies in G418 selective medium was markedly reduced and their morphology demonstrated changes toward a flattened and enlarged phenotype. Employing a high multiplicity of infection (MOI) with Lhp53RNL without neo(R) selection, the replication of wt p53-reconstituted cells was greatly reduced. The ability of the genetically modified cells to produce colonies in semi-solid medium and to form tumors in recipient nude mice was also markedly suppressed, Restoration of wt p53 expression in human breast cancer cells expressing endogenous mt (mutant) p53 can suppress some aspects of the malignant phenotype by a trans-dominant mechanism.