THE P53-BINDING PROTEIN MDM2 GENE IS DIFFERENTIALLY EXPRESSED IN HUMAN BREAST-CARCINOMA

The human p53-binding protein murine double minute 2 (MDM2) is believe d to function as a negative regulator of p53. The MDM2 gene was cloned and sequenced only recently and was found to be amplified in a variet y of sarcomas. Although mutations in the p53 gene have been shown to o ccur in human breast carcinoma (HBC), no information is available on M DM2 gene expression in HBC. In this study we report for the first time that the MDM2 gene is differentially expressed in HBC. Our results de monstrate a correlation between the estrogen receptor (ER) status and the MDM2 mRNA levels. In contrast to the ER-negative cell lines, all t he ER-positive cell lines were found to express higher levels of MDM2 mRNA. ER-positive ZR-75 cells express 30-fold higher levels of MDM2 mR NA than does the ER-negative cell line Hs578T. Estrogen enhanced albei t modestly the MDM2 mRNA levels in ER-positive MCF-7 cells. Estrogen e nhancement of MDM2 mRNA levels was also observed in ER-negative MDA-MB -231 cells transfected with functional ERs. Our data thus suggest that estrogen may play an important role in HBC growth stimulation by modu lating the expression of MDM2, which in turn may inactivate the p53 fu nction.