title: Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor.
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.
authors.affiliation: Department of Pathology, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Yueh-Chiang
authors.initials: YC
authors.lastname: Hu
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Xu
authors.forename: Meng-Yin
authors.initials: MY
authors.lastname: Tsai
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Dong
authors.forename: Ruey-Sheng
authors.initials: RS
authors.lastname: Wang
authors.forename: Ting-Hein
authors.initials: TH
authors.lastname: Lee
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis; D010641:Phenotype; D017526:Receptor, IGF Type 1 / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000032:analysis; D014158:Transcription, Genetic
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases