Kirma N, Gill K, Mandava U, Tekmal R R
Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia 30322, USA.
Cancer Res. 2001 Mar 1;61(5):1910-8.
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.
我们之前的研究表明，芳香化酶的过表达会导致组织雌激素活性增加，并在芳香化酶转基因乳腺中诱导增生性和发育异常性病变。在本研究中，我们检测了芳香化酶过表达对芳香化酶转基因小鼠生化变化的影响。我们的结果显示雌激素和孕激素受体的表达均增加，并且即使在没有循环卵巢雌激素的情况下，它们的表达仍在转基因乳腺组织中维持。我们的结果还显示，芳香化酶转基因乳腺中几种生长因子和细胞周期基因的表达增加，这与观察到的增殖细胞核抗原水平和细胞增殖增加一致。有趣的是，我们还观察到表皮生长因子受体及其配体表皮生长因子和转化生长因子α以及几种肿瘤抑制基因如p53和视网膜母细胞瘤的表达降低。本研究提出了新颖且有趣的发现，这些发现与当前芳香化酶影响模型以及导致乳腺肿瘤发生的生化途径的复杂相互作用一致。
