Overexpression of aromatase leads to hyperplasia and changes in the expression of genes involved in apoptosis, cell cycle, growth, and tumor suppressor functions in the mammary glands of transgenic mice.
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.
Kirma
N
N
Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia 30322, USA.
Gill
K
K
Mandava
U
U
Tekmal
R R
RR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006965:Hyperplasia / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000473:pathology* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004958:Estradiol; D001141:Aromatase