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PMID:14676301

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Citation

Yeh, S, Hu, YC, Wang, PH, Xie, C, Xu, Q, Tsai, MY, Dong, Z, Wang, RS, Lee, TH and Chang, C (2003) Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J. Exp. Med. 198:1899-908

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.

Links

PubMed PMC2194158 Online version:10.1084/jem.20031233

Keywords

Animals; Binding Sites; Cell Division; Cell Line, Tumor; DNA/metabolism; Female; Humans; Insulin-Like Growth Factor I/physiology; Male; Mammary Glands, Animal/growth & development; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases/metabolism; Morphogenesis; Phenotype; Receptor, IGF Type 1/physiology; Receptors, Androgen/physiology; Receptors, Estrogen/analysis; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ANDR

involved_in

GO:0043410: positive regulation of MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0043568: positive regulation of insulin-like growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0048009: insulin-like growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0060599: lateral sprouting involved in mammary gland duct morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0060748: tertiary branching involved in mammary gland duct morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0060749: mammary gland alveolus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0030520: intracellular estrogen receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0033148: positive regulation of intracellular estrogen receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

involved_in

GO:0000165: MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0060749: mammary gland alveolus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

results_in_development_of:(EMAPA:36566)

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0060748: tertiary branching involved in mammary gland duct morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

has_participant:(EMAPA:35538)

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0060599: lateral sprouting involved in mammary gland duct morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

has_participant:(EMAPA:35538)

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0033148: positive regulation of intracellular estrogen receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

regulates_o_occurs_in:(EMAPA:35538)

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0043410: positive regulation of MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

regulates_o_occurs_in:(EMAPA:35538)

Seeded From UniProt

complete

MOUSE:ANDR

acts_upstream_of_or_within

GO:0043568: positive regulation of insulin-like growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687199

P

regulates_o_occurs_in:(EMAPA:35538)

Seeded From UniProt

complete


See also

References

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