scholarly journals Transforming growth factor β's role in mammary gland development and carcinogenesis

2003 ◽  
Vol 5 (S1) ◽  
Author(s):  
MH Barcellos-Hoff
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
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 Attenuated TGFB signalling in macrophages decreases susceptibility to DMBA-induced mammary cancer in mice

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Xuan Sun ◽  
Sarah M. Bernhardt ◽  
Danielle J. Glynn ◽  
Leigh J. Hodson ◽  
Lucy Woolford ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Cancer ◽  
Breast Tissue ◽  
Mammary Gland Development ◽  
Transforming Growth Factor ◽  
Cancer Susceptibility ◽  
Dominant Negative ◽  
Target Cells ◽  
Tumour Development ◽  
Gland Development

AbstractBackgroundTransforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates mammary gland development and cancer progression through endocrine, paracrine and autocrine mechanisms. TGFB1 also plays roles in tumour development and progression, and its increased expression is associated with an increased breast cancer risk. Macrophages are key target cells for TGFB1 action, also playing crucial roles in tumourigenesis. However, the precise role of TGFB-regulated macrophages in the mammary gland is unclear. This study investigated the effect of attenuated TGFB signalling in macrophages on mammary gland development and mammary cancer susceptibility in mice.MethodsA transgenic mouse model was generated, wherein a dominant negative TGFB receptor is activated in macrophages, in turn attenuating the TGFB signalling pathway specifically in the macrophage population. The mammary glands were assessed for morphological changes through wholemount and H&E analysis, and the abundance and phenotype of macrophages were analysed through immunohistochemistry. Another cohort of mice received carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), and tumour development was monitored weekly. Human non-neoplastic breast tissue was also immunohistochemically assessed for latent TGFB1 and macrophage marker CD68.ResultsAttenuation of TGFB signalling resulted in an increase in the percentage of alveolar epithelium in the mammary gland at dioestrus and an increase in macrophage abundance. The phenotype of macrophages was also altered, with inflammatory macrophage markers iNOS and CCR7 increased by 110% and 40%, respectively. A significant decrease in DMBA-induced mammary tumour incidence and prolonged tumour-free survival in mice with attenuated TGFB signalling were observed. In human non-neoplastic breast tissue, there was a significant inverse relationship between latent TGFB1 protein and CD68-positive macrophages.ConclusionsTGFB acts on macrophage populations in the mammary gland to reduce their abundance and dampen the inflammatory phenotype. TGFB signalling in macrophages increases mammary cancer susceptibility potentially through suppression of immune surveillance activities of macrophages.

scholarly journals Re: Leptin--A Growth Factor in Normal and Malignant Breast Cells and for Normal Mammary Gland Development

2003 ◽  
Vol 95 (15) ◽  
pp. 1171-1173 ◽  
Author(s):  
E. Oelmann ◽  
S. Haghgu ◽  
E. Kulimova ◽  
H. Serve ◽  
C. Schmitmann ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Mammary Gland Development ◽  
Normal Mammary Gland ◽  
Malignant Breast ◽  
Breast Cells ◽  
Gland Development
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