Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.
Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.
复制标题
DOI：
10.1371/journal.pone.0113175
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kopelovich L
中科院分区：
文献类型：
--
作者：
Mehta RG;Hawthorne M;Mehta RR;Torres KE;Peng X;McCormick DL;Kopelovich L
本实验旨在确定雌激素受体α和β（ERα和ERβ）在小鼠乳腺正常和肿瘤发育中的作用。在野生型小鼠中，体内给予雌二醇（E）+黄体酮（P）刺激乳腺导管生长和肺泡分化。删除 ERβ 基因的小鼠（βERKO 小鼠）的乳腺在 E + P 反应中表现出正常的导管生长和分化。相比之下，删除 ERα 基因的小鼠（αERKO 小鼠）的乳腺仅表现出基本的导管结构，不会响应 E + P 分化。EGF 在乳腺中表现出雌激素样活性。 αERKO 小鼠的乳腺：用 EGF + P（无 E）治疗 αERKO 小鼠可支持正常乳腺发育，诱导孕酮受体 (PR) 表达，并增加 G 蛋白偶联受体 (GPR30) 蛋白水平。用 EGF + P 治疗的 βERKO 小鼠的乳腺发育与接受 EGF + P 治疗的野生型小鼠相当。 EGF 对野生型小鼠或 βERKO 小鼠乳腺中 PR 的诱导或 GPR30 的表达没有统计学上的显着影响。乳腺体外暴露于 7,12-二甲基苯并[a]蒽 (DMBA) 会在野生型小鼠和 βERKO 小鼠的腺体中诱导肿瘤前乳腺肺泡病变 (MAL)，但未能在 αERKO 小鼠的乳腺中诱导 MAL。对 DMBA 处理的乳腺进行微阵列分析，确定了 28 条功能通路，其表达在 αERKO 小鼠中与 βERKO 和野生型小鼠中显着不同； αERKO 小鼠差异表达的关键功能包括细胞分裂、细胞增殖和凋亡。这些数据证明了 ERα 和 ERβ 在小鼠乳腺正常和肿瘤发育中的不同作用，并表明 EGF 可以模仿 E 在该器官中的 ERα 介导的作用。
The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ.
登录
查看更多内容
支持雌激素受体β（ERβ）在ERα阳性乳腺癌细胞中的双重作用。
影响因子：
3.9
作者：
Jonsson P;Katchy A;Williams C
通讯作者：
Williams C
GPR30 作为激素依赖性乳腺癌他莫昔芬耐药的引发剂。
DOI：
10.1186/bcr3581
发表时间：
2013-11-29
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Mo Z;Liu M;Yang F;Luo H;Li Z;Tu G;Yang G
通讯作者：
Yang G
DOI：
10.1073/pnas.0307864100
发表时间：
2004-03-16
影响因子：
11.1
作者：
Cheng, GJ;Zhang, WH;Gustafsson, JA
通讯作者：
Gustafsson, JA
DOI：
10.1073/pnas.89.10.4658
发表时间：
1992-05-15
影响因子：
11.1
作者：
IGNARTROWBRIDGE, DM;NELSON, KG;KORACH, KS
通讯作者：
KORACH, KS
DOI：
10.1093/jnci/92.5.418
发表时间：
2000-03-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Mehta, RG;Williamson, E;Koeffler, HP
通讯作者：
Koeffler, HP