Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells.

Molecular and Cellular Biology
Natsumi HasegawaMitsuhiro Ito

Abstract

The Mediator subunit MED1 is essential for mammary gland development and lactation, whose contribution through direct interaction with estrogen receptors (ERs) is restricted to involvement in pubertal mammary gland development and luminal cell differentiation. Here, we provide evidence that the MED24-containing submodule of Mediator functionally communicates specifically with MED1 in pubertal mammary gland development. Mammary glands from MED1/MED24 double heterozygous knockout mice showed profound retardation in ductal branching during puberty, while single haploinsufficient glands developed normally. DNA synthesis of both luminal and basal cells were impaired in double mutant mice, and the expression of ER-targeted genes encoding E2F1 and cyclin D1, which promote progression through the G(1)/S phase of the cell cycle, was attenuated. Luciferase reporter assays employing double mutant mouse embryonic fibroblasts showed selective impairment in ER functions. Various breast carcinoma cell lines expressed abundant amounts of MED1, MED24, and MED30, and attenuated expression of MED1 and MED24 in breast carcinoma cells led to attenuated DNA synthesis and growth. These results indicate functional communications between the MED1 subun...Continue Reading

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Citations

Nov 20, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shumpei MizutaMitsuhiro Ito
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Sep 3, 2019·EMBO Molecular Medicine·Abir ArfaouiChristophe Ginestier
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Sep 12, 2018·Molecular Genetics and Genomics : MGG·Xiaoyong PanYu-Dong Cai
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Nov 22, 2017·Steroids·Hannah Weber, Michael J Garabedian
Jul 30, 2015·Genes & Development·Artyom A AlekseyenkoChristopher A French

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