Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer.
Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer.
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DOI：
10.1186/1471-2407-13-573
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发表时间：
2013-12-05
期刊：
影响因子：
3.8
通讯作者：
Shull JD
中科院分区：
文献类型：
--
作者：
Ding L;Zhao Y;Warren CL;Sullivan R;Eliceiri KW;Shull JD
我们使用 ACI 和 BN 大鼠来鉴定决定乳腺癌易感性的遗传变异和环境因素，它们对 17β-雌二醇 (E2) 诱发的乳腺癌的易感性存在显着差异。本研究的目的是表征 ACI 和 BN 大鼠乳腺对 E2 的细胞和分子反应，以确定与乳腺癌易感性相关和/或可能赋予差异的定性和定量表型。雌性 ACI 和 BN 大鼠用 E2 治疗 1、3 或 12 周。通过整体封片和苏木精和伊红 (H&E) 染色检查乳腺形态和组织学。通过定量免疫组织化学评估细胞增殖和上皮密度。通过定量蛋白质印迹和流式细胞术评估细胞凋亡。通过免疫组织化学检查乳腺分化。通过微阵列、qRT-PCR 和定量蛋白质印迹分析评估基因表达。通过天狼星红染色和二次谐波发生（SHG）显微镜评估细胞外基质（ECM）相关的胶原蛋白。 ACI 大鼠的管腔上皮对 E2 表现出快速且持续的增殖反应。相比之下，BN 大鼠的乳腺上皮表现出的增殖反应是有限且短暂的。此外，BN 大鼠的上皮似乎因 E2 的反应而发生分化，乳蛋白的产生以及管腔扩张和 ECM 的相关变化证明了这一点。编码在乳腺发育（Pgr、Wnt4、Tnfsf11、Prlr、Stat5a、Areg、Gata3）、分化和产奶（Lcn2、Spp1）、细胞外环境调节（Mmp7、Mmp9）以及细胞-细胞或细胞-ECM相互作用（Cd44、Cd24、Cd52）中具有明确作用的蛋白质的基因表达存在显着差异。我们认为这些细胞和分子表型是可遗传的，并且可能至少部分地是 ACI 和 BN 大鼠所表现出的乳腺癌易感性差异的基础。
We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in part, the differences in mammary cancer susceptibility exhibited by ACI and BN rats.
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影响因子：
5.3
作者：
Gonzalez-Suarez, Eva;Branstetter, Daniel;Dougall, William C.
通讯作者：
Dougall, William C.
DOI：
10.1093/jnci/87.21.1622
发表时间：
1995-11-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
BYRNE, C;SCHAIRER, C;HAILE, R
通讯作者：
HAILE, R
影响因子：
64.8
作者：
Asselin-Labat, Marie-Liesse;Vaillant, Francois;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
9.7
作者：
DELP, CR;TREVES, JS;BANERJEE, MR
通讯作者：
BANERJEE, MR
影响因子：
--
作者：
D'Cruz, CM;Moody, SE;Chodosh, LA
通讯作者：
Chodosh, LA