An in vivo model of intratumoural aromatase using aromatase‐transfected MCF7 human breast cancer cells

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Abstract
About two-thirds of human breast carcinomas contain detectable levels of aromatase, the enzyme which converts androgens to oestrogens. Assessment of the importance of this enzyme to breast cancer growth has been hampered by the absence of an adequate model system. We have previously reported that MCF7 human hormone-dependent breast cancer cells transfected with human aromatase cDNA (Aram I cells) showed a growth response in vitro to exogenous androgens and this effect was blocked by aromatase inhibitors. We report here our use of these cells to develop a xenograft model in athymic nude mice. Neither MCF7 cells nor Aram 1 cells formed tumours in oophorectomised (ovx) nude mice unless provided with oestradiol (E2) support. Once established, Aram 1, but not MCF7, tumours could be grown in ovx females supplemented with androstenedione (Δ4A). The mean plasma level of Δ4A was 14 nmol/L in supplemented animals and < 0.5 nmol/L in unsupplemented animals. Similarly, unsupplemented male nude mice were able to support the growth of Aram 1 tumours but not MCF7 tumours. The potent and highly specific aromatase inhibitor CGS20267 (letrozole) significantly decreased tumour growth at 2 mg/kg/day and completely inhibited growth at 20 mg/kg/day in Δ4A-supplemented but not E2-supplemented animals. Our results indicate that Δ4A-dependent growth of Arom 1 tumours in vivo is mediated through the action of intratumoural aromatase. This model should allow an assessment of the critical levels of aromatase required for tumour growth support. © 1995 Wiley-Liss Inc.

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