AN IN-VIVO MODEL OF INTRATUMORAL AROMATASE USING AROMATASE-TRANSFECTED MCF7 HUMAN BREAST-CANCER CELLS

About two-thirds of human breast carcinomas contain detectable levels of aromatase, the enzyme which converts androgens to oestrogens. Asses sment of the importance of this enzyme to breast cancer growth has bee n hampered by the absence of an adequate model system. We have previou sly reported that MCF7 human hormone-dependent breast cancer cells tra nsfected with human aromatase cDNA (Arom1 cells) showed a growth respo nse in vitro to exogenous androgens and this effect was blocked by aro matase inhibitors. We report here our use of these cells to develop a xenograft model in athymic nude mice. Neither MCF7 cells nor Arom I ce lls formed tumours in oophorectomised (ovx) nude mice unless provided with oestradiol (E2) support. Once established, Arom1, but not MCF7, t umours could be grown in ovx females supplemented with androstenedione (Delta 4A). The mean plasma level of Delta 4A was 14 nmol/L in supple mented animals and < 0.5 nmol/L in unsupplemented animals. Similarly, unsupplemented male nude mice were able to support the growth of Arom1 tumours but not MCF7 tumours. The potent and highly specific aromatas e inhibitor CGS20267 (letrozole) significantly decreased tumour growth at 2 mg/kg/day and completely inhibited growth at 20 mg/kg/day in Del ta 4A-supplemented but not E2-supplemented animals. Our results indica te that Delta 4A-dependent growth of Arom1 tumours in vivo is mediated through the action of intratumoural aromatase. This model should allo w an assessment of the critical levels of aromatase required for tumou r growth support. (C) 1995 Wiley-Liss, Inc.