Altered P53 conformation.

The p53 protein is a transcription factor that is frequently mutated in human malignancies. Using the MCF10AT model for early human breast cancer we show that P53 protein is unmutated indicating that mutations are not necessary for alterations in growth and morphology that accompany preneoplastic stages of breast tumor progression. Although p53 protein is wild-type in cells of the MCF10AT model system, it exists predominantly in a conformationally altered state that is defective in its ability both to bind DNA in a sequence-specific manner and to induce transcriptional activation from the WAF-1 promoter. This contrasts with P53 from the non-tumorigenic parental MCF10A cells which is predominantly conformationally normal and functionally active. The possibility that stabilized wild-type but conformationally altered P53 plays a role in the neoplastic progression of preneoplastic MCF10AT system cells is discussed.