Dataset Information

Differential roles of ER? and ER? in normal and neoplastic development in the mouse mammary gland.

ABSTRACT: The present experiments were performed to determine the roles of estrogen receptors ? and ? (ER? and ER?) 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 ER? gene has been deleted (?ERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ER? gene has been deleted (?ERKO 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 ?ERKO mice: treatment of ?ERKO 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 ?ERKO 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 ?ERKO 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 ?ERKO mice, but failed to induce MAL in mammary glands from ?ERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in ?ERKO mice versus both ?ERKO and wild-type mice; key functions that were differentially expressed in ?ERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ER? and ER? in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ER?-mediated effects of E in this organ.

SUBMITTER: Mehta RG

PROVIDER: S-EPMC4236140 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.

Mehta Rajendra G RG Hawthorne Michael M Mehta Rajeshwari R RR Torres Karen E O KE Peng Xinjian X McCormick David L DL Kopelovich Levy L

PloS one 20141118 11

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 mi ...[more]

PMID: 25405629

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Project description:The present experiments were performed to determine the roles of estrogen receptors M-NM-1 and M-NM-2 (ERM-NM-1 and ERM-NM-2) 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 ERM-NM-2 gene has been deleted (M-NM-2ERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERM-NM-1 gene has been deleted (M-NM-1ERKO 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 M-NM-1ERKO mice: treatment of M-NM-1ERKO 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 M-NM-2ERKO 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 M-NM-2ERKO 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 M-NM-2ERKO mice, but failed to induce MAL in mammary glands from M-NM-1ERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in M-NM-1ERKO mice versus both M-NM-2ERKO and wild-type mice; key functions that were differentially expressed in M-NM-1ERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERM-NM-1 and ERM-NM-2 in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERM-NM-1-mediated effects of E in this organ. Gene expression of mammary gland organ culture and DMBA-induced lesions from 4 mouse strains.

Dataset Information

Differential roles of ER? and ER? in normal and neoplastic development in the mouse mammary gland.

Publications

Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.

Similar Datasets

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