BIOLOGICAL EFFECTS OF STABLE OVEREXPRESSION OF AROMATASE IN HUMAN HORMONE-DEPENDENT BREAST-CANCER CELLS

Aromatase is a key enzyme in the conversion of androstenedione and tes tosterone to oestrone and oestradiol. Intratumoral aromatase activity is expressed by around 70% of breast carcinomas, but it is not clear w hat effect this has on the tumour phenotype. To address this question we expressed human aromatase in hormone-dependent MCF-7 breast cancer cells. Clone Arom. 1 expressed aromatase al 1,000 times the endogenous level in wild-type (WT) cells. Clone Arom. 2 incorporated the express ion construct but did not express aromatase at levels above WT. There was no morphological difference between the two clones and WT, all thr ee cell lines expressed oestrogen receptor at equivalent levels, and a ll manifested a mitogenic response to oestradiol. In steroid-depleted medium Arom. 1 cells showed significant growth enhancement over WT and Arom. 2, and this growth advantage was increased by exogenous androst enedione or testosterone. Both the enzyme activity and androgen-stimul ated growth of Arom. 1 cells were completely reversible by aromatase i nhibitor CGS 16949A. The Arom. 1 cell line may contribute to the devel opment of an in vivo model of intratumoral aromatase, to study the bio logical significance of this phenomenon.