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J Steroid Biochem Mol Biol 44: 321–330 70 Simpson ER, Ackerman GE, Smith ME, Mendelson CR (1981) Estrogen formation in stromal cells of adipose tissue of women: Induction of glucocorticosteroids. Proc Natl Acad Sci USA 78: 5690–5694 71 Johnston JO, Wright CL, Schumaker RC (1989) Human trophoblast xenografts in athymic mice: a model for peripheral aromatization. J Steroid Biochem Mol Biol 33: 521–529 72 Franz C, Longcope C (1979) Androgen and estrogen metabolism in male Rhesus monkeys. Endocrinology 105: 869–874 73 Lonning PE, Geisler J, Bhatnagar A (2003) Development of aromatase inhibitors and their pharmacological profile.
J Steroid Biochem Mol Biol 95: 41–48 Sabnis GJ, Jelovac D, Long B, Brodie A (2005) The role of growth factor receptor pathways in human breast cancer cells adapted to long term estrogen deprivation.
Consistent with these findings, studies by Fisher et al. [38], have shown that oestrogen deficiency in aromatase-knockout mice leads to underdeveloped genitalia and immature mammary glands. Although the mammary glands of female aromatase-transgenic mice exhibited hyperplastic and dysplastic changes, palpable mammary tumours have not been observed even in animals more than 2 years old. This suggests that other cooperating factor(s) or carcinogenic events are required for development of cancer. Thus administration of a single dose of dimethyl-benzanthracene Aromatase inhibitors and models for breast cancer 27 (DMBA) resulted in the induction of frank mammary tumours in about 25% of aromatase-transgenic mice, and all animals had microscopic evidence of tumour formation, whereas there was no evidence of tumours in DMBA-treated non-transgenic mice [43].