scholarly journals Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis

2016 ◽  
Vol 30 (3) ◽  
pp. 278-289 ◽  
Author(s):  
Yan Zuo ◽  
Wonkyung Oh ◽  
Arzu Ulu ◽  
Jeffrey A. Frost
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Rho Gtpase ◽  
Cultured Cells ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Normal Mammary Gland ◽  
Rho Proteins ◽  
And Function ◽  
Gland Development

Abstract Ras homolog (Rho) family small GTPases are critical regulators of actin cytoskeletal organization, cell motility, proliferation, and survival. Surprisingly, the large majority of the studies underlying our knowledge of Rho protein function have been carried out in cultured cells, and it is only recently that researchers have begun to assess Rho GTPase regulation and function in vivo. The purpose of this review is to evaluate our current knowledge of Rho GTPase function in mouse mammary gland development, tumorigenesis and metastasis. Although our knowledge is still incomplete, these studies are already uncovering important themes as to the physiological roles of Rho GTPase signaling in normal mammary gland development and function. Essential contributions of Rho proteins to breast cancer initiation, tumor progression, and metastatic dissemination have also been identified.

scholarly journals Mammary Gland Specific Knockdown of the Physiological Surge in Cx26 during Lactation Retains Normal Mammary Gland Development and Function

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101546 ◽  
Author(s):  
Michael K. G. Stewart ◽  
Isabelle Plante ◽  
John F. Bechberger ◽  
Christian C. Naus ◽  
Dale W. Laird
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Normal Mammary Gland ◽  
And Function ◽  
Gland Development

scholarly journals Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1351 ◽  
Author(s):  
Nora Jung ◽  
Veronique Maguer-Satta ◽  
Boris Guyot
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mammary Gland ◽  
Bone Morphogenetic Proteins ◽  
Mammary Gland Development ◽  
Cell Transformation ◽  
Current Knowledge ◽  
Endocrine Disrupting Chemicals ◽  
Normal Mammary Gland ◽  
Gland Development

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.

scholarly journals Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Parisa Rabieifar ◽  
Ting Zhuang ◽  
Tânia D. F. Costa ◽  
Miao Zhao ◽  
Staffan Strömblad
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Small Gtpases ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Adult Mice ◽  
Gland Development

Abstract p21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.

scholarly journals Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion

2019 ◽  
Author(s):  
Parisa Rabieifar ◽  
Ting Zhuang ◽  
Tânia D. F. Costa ◽  
Miao Zhao ◽  
Staffan Strömblad
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Small Gtpases ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Adult Mice ◽  
Gland Development

Abstractp21-activated protein kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model for examination of the potential function of PAK4 in breast cancer.

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.

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