Harvell D M, Strecker T E, Tochacek M, Xie B, Pennington K L, McComb R D, Roy S K, Shull J D
Eppley Institute for Research in Cancer, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2779-84. doi: 10.1073/pnas.050569097.
The genetically related ACI and Copenhagen (COP) rat strains display diametrically opposed susceptibilities to mammary cancer development when treated chronically with 17beta-estradiol (E2). Here, we compare the actions of E2 on cell proliferation and lobuloalveolar development in the mammary glands of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glands of ACI rats exhibited a significantly greater proliferative response to E2, compared with COP rats, as evidenced by quantification of S phase fraction and development of lobuloalveolar hyperplasia. Focal regions of atypical epithelial hyperplasia were observed in ACI, but not COP, rats. These strain differences were not because of differences in circulating E2, progesterone or, prolactin. Two-thirds of the induced mammary cancers in ACI rats exhibited aneuploidy. The E2-induced mammary cancers regressed when hormone treatment was discontinued, indicating that they were estrogen-dependent. Progesterone receptor was expressed by the great majority of epithelial cells within the E2-induced atypical hyperplastic foci and the mammary carcinomas, suggesting a link between these lesions. These data demonstrate a correlation between E2 action in the induction of mammary cell proliferation and atypical epithelial hyperplasia and genetically conferred susceptibility to E2-induced mammary cancers.
当长期用17β-雌二醇（E2）处理时，遗传相关的ACI和哥本哈根（COP）大鼠品系对乳腺癌发生表现出截然相反的易感性。在此，我们比较了E2对雌性ACI和COP大鼠乳腺细胞增殖和小叶腺泡发育的作用。E2处理12周后，与COP大鼠相比，ACI大鼠的乳腺对E2表现出显著更强的增殖反应，这通过S期比例的定量和小叶腺泡增生的发展得以证明。在ACI大鼠而非COP大鼠中观察到非典型上皮增生的局灶区域。这些品系差异并非由于循环E2、孕酮或催乳素的差异。ACI大鼠中三分之二的诱导性乳腺癌表现出非整倍体。当停止激素处理时，E2诱导的乳腺癌消退，表明它们是雌激素依赖性的。E2诱导的非典型增生灶和乳腺癌内的绝大多数上皮细胞表达孕酮受体，提示这些病变之间存在联系。这些数据证明了E2在诱导乳腺细胞增殖和非典型上皮增生中的作用与遗传赋予的对E2诱导的乳腺癌易感性之间的相关性。
