MDM2 overexpression in benign and malignant lesions of the human breast.

MDM2 overexpression has been detected in women with benign or cancerous lesions of the breast. Immunohistochemical methods were used to identify overexpression in 11 of 27 benign cases (41%) and 15 of 22 (68%) cancer cases. MDM2 overexpression correlated well with immunohistochemically detected estrogen receptor (ER), suggesting that expression of these proteins was coordinately regulated. To test this, the MCF-10A human breast cell line, negative for both ER and MDM2 expression, was transfected with a wild-type ER. Following transfection, both ER and MDM2 were strongly expressed in two independent clones. Expression of both was reduced in the presence of increasing concentrations of estradiol (10(-10)-10(-8) M) thus, estrogen may be involved in regulation of MDM2 expression in proliferative breast lesions.