Pvm. Shekhar et al., ALTERED P53 CONFORMATION - A NOVEL MECHANISM OF WILD-TYPE P53 FUNCTIONAL INACTIVATION IN A MODEL FOR EARLY HUMAN BREAST-CANCER, International journal of oncology, 11(5), 1997, pp. 1087-1094
The p53 protein is a transcription factor that is frequently mutated i
n human malignancies. Using the MCF10AT model for early human breast c
ancer we show that P53 protein is unmutated indicating that mutations
are not necessary for alterations in growth and morphology that accomp
any preneoplastic stages of breast tumor progression. Although p53 pro
tein is wild-type in cells of the MCF10AT model system, it exists pred
ominantly 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 wit
h P53 from the non-tumorigenic parental MCF10A cells which is predomin
antly conformationally normal and functionally active. The possibility
that stabilized wild-type but conformationally altered P53 plays a ro
le in the neoplastic progression of preneoplastic MCF10AT system cells
is discussed.