Abnormal Mammary Gland Development and Growth Retardation in Female Mice and MCF7 Breast Cancer Cells Lacking Androgen Receptor

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2003 Dec 17

PMID 14676301

Citations 52

Authors

Shuyuan Yeh

Yueh-Chiang Hu

Peng-Hui Wang

Chao Xie

Qingquan Xu

Meng-Yin Tsai

Zhihong Dong

Ruey-Sheng Wang

Ting-Hein Lee

Chawnshang Chang

Affiliations

Soon will be listed here.

Abstract

Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR-/-) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR-/- mammary glands involves the defects of insulin-like growth factor I-insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor-mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR-/- MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation.

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