Abstract
Our previous studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in aromatase transgenic mammary glands. In this study, we have examined the effects of aromatase overexpression on biochemical changes in the aromatase transgenic mice. Our results show an increase in the expression of both estrogen and progesterone receptors, and their expression is maintained in the transgenic mammary tissue even without circulating ovarian estrogens. Our results also show an increase in the expression of several growth factors and cell cycle genes in the aromatase transgenic mammary glands, which is consistent with the observed increase in proliferating cell nuclear antigen levels and cellular proliferation. Interestingly, we have also observed a decrease in the expression of epidermal growth factor receptor and its ligands, epidermal growth factor and transforming growth factor alpha, as well as several tumor suppressor genes such as p53 and retinoblastoma. This study presents novel and interesting findings that are consistent with the current models of aromatase influence and the complex interactions of biochemical pathways leading to mammary tumorigenesis.
Publication types
-
Comparative Study
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Apoptosis / genetics*
-
Aromatase / biosynthesis*
-
Aromatase / genetics
-
Cell Cycle / genetics
-
Cell Division / genetics
-
Estradiol / blood
-
Female
-
Gene Expression Regulation
-
Genes, Tumor Suppressor / genetics*
-
Growth Substances / biosynthesis
-
Growth Substances / genetics
-
Hyperplasia / enzymology
-
Mammary Glands, Animal / enzymology*
-
Mammary Glands, Animal / pathology*
-
Mammary Glands, Animal / physiology
-
Mammary Neoplasms, Experimental / enzymology
-
Mammary Neoplasms, Experimental / genetics
-
Mammary Neoplasms, Experimental / pathology
-
Mice
-
Mice, Transgenic
-
Precancerous Conditions / enzymology
-
Precancerous Conditions / genetics
-
Precancerous Conditions / pathology
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
-
Proto-Oncogene Proteins c-bcl-2 / genetics
-
Receptors, Estrogen / biosynthesis
-
Receptors, Estrogen / genetics
-
Receptors, Progesterone / biosynthesis
-
Receptors, Progesterone / genetics
-
bcl-2-Associated X Protein
-
bcl-X Protein
Substances
-
Bcl2l1 protein, mouse
-
Growth Substances
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Receptors, Estrogen
-
Receptors, Progesterone
-
bcl-2-Associated X Protein
-
bcl-X Protein
-
Estradiol
-
Aromatase