TY - JOUR
T1 - Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice
AU - Luthra, Roopa
AU - Kirma, Nameer
AU - Jones, Jeremy
AU - Tekmal, Rajeshwar Rao
N1 - Funding Information:
This work was supported by a grant from NIH/NCI CA 75018 and a research Grant from Novartis Pharma AG, Basel. Switzerland. The authors thank Dr. Neil Sidell for helpful discussion in preparation of this manuscript.
PY - 2003/9
Y1 - 2003/9
N2 - Our recent studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in mammary glands, and gynecomastia and testicular cancer in male aromatase transgenic mice. Our studies also have shown that aromatase overexpression-induced changes in mammary glands can be abrogated with very low concentrations of letrozole, an aromatase inhibitor without any effect on normal physiology. In the present study, we have examined the effect of prior low dose letrozole treatment on pregnancy and lactation. We have also investigated the effect of low dose letrozole treatment on subsequent mammary growth and biochemical changes in these animals. There was no change in the litter size, birth weight and no visible birth defects in letrozole-treated animals. Although, there was an insignificant increase in mammary growth in aged animals after 6 weeks of letrozole treatment, the levels of expression of estrogen receptor, progesterone receptor and genes involved in cell cycle and cell proliferation remained low compared to control untreated animals. These observations indicate that aromatase inhibitors such as letrozole can be used as chemopreventive agents without effecting normal physiology in aromatase transgenic mice.
AB - Our recent studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in mammary glands, and gynecomastia and testicular cancer in male aromatase transgenic mice. Our studies also have shown that aromatase overexpression-induced changes in mammary glands can be abrogated with very low concentrations of letrozole, an aromatase inhibitor without any effect on normal physiology. In the present study, we have examined the effect of prior low dose letrozole treatment on pregnancy and lactation. We have also investigated the effect of low dose letrozole treatment on subsequent mammary growth and biochemical changes in these animals. There was no change in the litter size, birth weight and no visible birth defects in letrozole-treated animals. Although, there was an insignificant increase in mammary growth in aged animals after 6 weeks of letrozole treatment, the levels of expression of estrogen receptor, progesterone receptor and genes involved in cell cycle and cell proliferation remained low compared to control untreated animals. These observations indicate that aromatase inhibitors such as letrozole can be used as chemopreventive agents without effecting normal physiology in aromatase transgenic mice.
KW - Aromatase
KW - Aromatase inhibitors
KW - Chemoprevention
KW - Tamoxifen
KW - Transgenic mice
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U2 - 10.1016/S0960-0760(03)00358-3
DO - 10.1016/S0960-0760(03)00358-3
M3 - Article
C2 - 14623545
AN - SCOPUS:0242626109
SN - 0960-0760
VL - 86
SP - 461
EP - 467
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 3-5
ER -