ABNORMAL EXPRESSION OF MDM-2 IN BREAST CARCINOMAS

MDM-2 is a cellular oncoprotein that binds to the p53 protein and abro gates its growth-suppressing function. At least seven MDM-2 mRNAs and five proteins (p90, p85, p76, p74, and p57) have been reported in tiss ue culture. MDM-2 gene amplification occurs in human sarcomas and high -grade gliomas. MDM-2 overexpression without gene amplification has be en reported in leukemias and lymphomas. Here we report MDM-2 mRNA over expression in 24 (73%) out of 33 cases of human breast carcinoma as co mpared with normal breast tissue. The MDM-2 overexpression was seen in the absence of MDM-2 gene amplification. MDM-2 protein expression was studied by western blot analysis in 21 of these cases of carcinoma. W e found complete concordance between MDM-2 mRNA overexpression and MDM -2 protein levels. MDM-2 proteins were overexpressed in 15 of 21 breas t carcinoma tissue samples but not in normal breast tissue controls. T en of these fifteen cases overexpressed MDM-2 p57 protein, two cases o verexpressed both p57 and p90, and three cases overexpressed only p90. MDM-2 overexpression was confirmed by immunohistochemistry. p53 overe xpression was also studied by immunohistochemistry; 69% of breast carc inomas that overexpressed the MDM-2 mRNA had detectable nuclear p53 pr otein. These findings demonstrate that MDM-2 oncoprotein expression is altered in primary human breast carcinomas at both mRNA and protein l evels. In addition, our results suggest that MDM-2 p57 protein represe nts the main MDM-2 protein altered in breast carcinomas.