In Vivo Structure-Function Studies on the Precise Role of ErbB-2 Signaling in Mammary Gland Development

2003 ◽  
Author(s):  
Richard Chan ◽  
William J. Muller
Keyword(s):  
Mammary Gland ◽  
Structure Function ◽  
Mammary Gland Development ◽  
Gland Development ◽  
Precise Role

scholarly journals The Role of Csmd1 during Mammary Gland Development

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 162
Author(s):  
Samuel J. Burgess ◽  
Hannah Gibbs ◽  
Carmel Toomes ◽  
Patricia L. Coletta ◽  
Sandra M. Bell
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Expression Patterns ◽  
Development In Vitro ◽  
Duct Development ◽  
Gland Development ◽  
Ductal Development

The Cub Sushi Multiple Domains-1 (CSMD1) protein is a tumour suppressor which has been shown to play a role in regulating human mammary duct development in vitro. CSMD1 knockdown in vitro demonstrated increased cell proliferation, invasion and motility. However, the role of Csmd1 in vivo is poorly characterised when it comes to ductal development and is therefore an area which warrants further exploration. In this study a Csmd1 knockout (KO) mouse model was used to identify the role of Csmd1 in regulating mammary gland development during puberty. Changes in duct development and protein expression patterns were analysed by immunohistochemistry. This study identified increased ductal development during the early stages of puberty in the KO mice, characterised by increased ductal area and terminal end bud number at 6 weeks. Furthermore, increased expression of various proteins (Stat1, Fak, Akt, Slug/Snail and Progesterone receptor) was shown at 4 weeks in the KO mice, followed by lower expression levels from 6 weeks in the KO mice compared to the wild type mice. This study identifies a novel role for Csmd1 in mammary gland development, with Csmd1 KO causing significantly more rapid mammary gland development, suggesting an earlier adult mammary gland formation.

scholarly journals Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3577-3588 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Kyle T. Smith ◽  
Anastasia Kariagina ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Minor Role ◽  
Normal Mammary Gland ◽  
Temporal Separation ◽  
Stage Of Development ◽  
Gland Development

Abstract Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2′-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.

Role of the Placenta in Mammary Gland Development and Function

1987 ◽  
pp. 459-498 ◽  
Author(s):  
Gudmundur Thordarson ◽  
Frank Talamantes
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
And Function ◽  
Gland Development

scholarly journals Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3442-3450 ◽  
Author(s):  
Cathrin Brisken ◽  
Kathryn Hess ◽  
Rachel Jeitziner
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Hormone Receptor ◽  
Cell Activation ◽  
Mammary Gland Development ◽  
Breast Cancer Incidence ◽  
Menstrual Cycles ◽  
Hormone Receptor Positive ◽  
Gland Development

Worldwide, breast cancer incidence has been increasing for decades. Exposure to reproductive hormones, as occurs with recurrent menstrual cycles, affects breast cancer risk, and can promote disease progression. Exogenous hormones and endocrine disruptors have also been implicated in increasing breast cancer incidence. Numerous in vitro studies with hormone-receptor-positive cell lines have provided insights into the complexities of hormone receptor signaling at the molecular level; in vivo additional layers of complexity add on to this. The combined use of mouse genetics and tissue recombination techniques has made it possible to disentangle hormone action in vivo and revealed that estrogens, progesterone, and prolactin orchestrate distinct developmental stages of mammary gland development. The 2 ovarian steroids that fluctuate during menstrual cycles act on a subset of mammary epithelial cells, the hormone-receptor-positive sensor cells, which translate and amplify the incoming systemic signals into local, paracrine stimuli. Progesterone has emerged as a major regulator of cell proliferation and stem cell activation in the adult mammary gland. Two progesterone receptor targets, receptor activator of NfκB ligand and Wnt4, serve as downstream paracrine mediators of progesterone receptor-induced cell proliferation and stem cell activation, respectively. Some of the findings in the mouse have been validated in human ex vivo models and by next-generation whole-transcriptome sequencing on healthy donors staged for their menstrual cycles. The implications of these insights into the basic control mechanisms of mammary gland development for breast carcinogenesis and the possible role of endocrine disruptors, in particular bisphenol A in this context, will be discussed below.

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