scholarly journals Transforming growth factor-β and breast cancer: Mammary gland development

10.1186/bcr40 ◽  
2000 ◽  
Vol 2 (2) ◽  
Author(s):  
Mary Helen Barcellos-Hoff ◽  
Kenneth BR Ewan
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Growth Factor ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gland Development

scholarly journals A Functional Connection between pRB and Transforming Growth Factor β in Growth Inhibition and Mammary Gland Development

2009 ◽  
Vol 29 (16) ◽  
pp. 4455-4466 ◽  
Author(s):  
Sarah M. Francis ◽  
Jacqueline Bergsied ◽  
Christian E. Isaac ◽  
Courtney H. Coschi ◽  
Alison L. Martens ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Mammary Development ◽  
Functional Connection ◽  
Gland Development

ABSTRACT Transforming growth factor β (TGF-β) is a crucial mediator of breast development, and loss of TGF-β-induced growth arrest is a hallmark of breast cancer. TGF-β has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-β cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1 ΔL and Rb1NF ), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-β growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-β signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-β cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-β in growth control and mammary gland development.

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

2003 ◽  
Vol 198 (12) ◽  
pp. 1899-1908 ◽  
Author(s):  
Shuyuan Yeh ◽  
Yueh-Chiang Hu ◽  
Peng-Hui Wang ◽  
Chao Xie ◽  
Qingquan Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Androgen Receptor ◽  
Growth Factor ◽  
Growth Retardation ◽  
Breast Cancer Cells ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Factor I ◽  
Gland Development

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.

Versican G1 and G3 domains are upregulated and latent transforming growth factor-β binding protein-4 is downregulated in breast cancer stroma

Breast Cancer ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Yuko Takahashi ◽  
Hiroko Kuwabara ◽  
Masahiko Yoneda ◽  
Zenzo Isogai ◽  
Nobuhiko Tanigawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β ◽  
Cancer Stroma
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