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.

scholarly journals Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium

2000 ◽  
Vol 113 (12) ◽  
pp. 2129-2138 ◽  
Author(s):  
S. Naylor ◽  
M.J. Smalley ◽  
D. Robertson ◽  
B.A. Gusterson ◽  
P.A. Edwards ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Ectopic Expression ◽  
Mammary Epithelium ◽  
Mouse Mammary Gland ◽  
Normal Mammary Gland ◽  
Gland Development

Several Wnt genes are expressed in the postnatal mouse mammary gland and are thought to be involved in mammary gland development. Ectopic expression of Wnt-1, which is not normally expressed in the mammary gland, drives the formation of a pre-neoplastic hyperplasia. Cell culture-based assays have shown that Wnt-1 and some mammary-expressed Wnts transform C57MG cells. This has led to the suggestion that Wnt-1 functions as an oncogene through the inappropriate activation of developmental events that are normally controlled by the ‘transforming’ class of Wnts. In this study, Wnt-7b was expressed in vivo using recombinant retroviruses. Wnt-7b did not alter normal mammary gland development despite having similar effects to Wnt-1 in cell culture. We conclude that the in vitro classification of Wnts as ‘transforming’ does not correlate with the transformation in vivo. To facilitate the analysis of Wnt-expression, a lacZ-containing, bicistronic recombinant retrovirus was developed. Immunohistochemistry and electron microscopy identified retrovirally transduced myoepithelial and luminal epithelial cells in normal and hyperplastic tissues. The distribution of transduced cells in mammary outgrowths was consistent with current models of mammary stem cell identity.

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 Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation

2017 ◽  
Vol 312 (3) ◽  
pp. E136-E149 ◽  
Author(s):  
Khanh Pham ◽  
Jie Dong ◽  
Xiqian Jiang ◽  
Ying Qu ◽  
Han Yu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Redox Homeostasis ◽  
Physiological Role ◽  
Cell Types ◽  
Normal Mammary Gland ◽  
Pregnancy And Lactation ◽  
Gland Development ◽  
Lobuloalveolar Development

Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of Grx3 at pregnancy and lactation stages. To assess the physiological role of Grx3 in MG, we generated the mutant mice in which Grx3 was deleted specifically in mammary epithelial cells (MECs). Although the reduction of Grx3 expression had only minimal effects on mammary ductal development in virgin mice, it did reduce alveolar density during pregnancy and lactation. The impairment of lobuloalveolar development was associated with high levels of ROS accumulation and reduced expression of milk protein genes. In addition, proliferative gene expression was significantly suppressed with proliferation defects occurring in knockout MECs during alveolar development compared with wild-type controls. Therefore, our findings suggest that Grx3 is a key regulator of ROS in vivo and is involved in pregnancy-dependent mammary gland development and secretory activation through modulating cellular ROS.

scholarly journals Progesterone Receptor Isoforms and Proliferation in the Rat Mammary Gland during Development

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2723-2736 ◽  
Author(s):  
Anastasia Kariagina ◽  
Mark D. Aupperlee ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Mammary Gland Development ◽  
Kinase Inhibitors ◽  
Expression Patterns ◽  
Significant Proportion ◽  
Myoepithelial Cells ◽  
Normal Mammary Gland ◽  
Rat Mammary Gland ◽  
Gland Development

Progesterone (P), acting through progesterone receptor (PR) isoforms A and B, plays an important role in normal mammary gland development and is implicated in the etiology of breast cancer. Because of significant similarities between human and rat mammary gland development and hormonal responsiveness of mammary cancers, we investigated P action in the rat mammary gland. By immunohistochemical methods we determined PRA and PRB expression at puberty, sexual maturity, pregnancy, and lactation and after postlactational involution and their functional roles in the regulation of proliferation. PRA expression was restricted to luminal epithelial cells, whereas PRB was expressed in both luminal and myoepithelial cells, indicating a novel role of PRB in myoepithelial cell regulation. The majority of PRA-positive (PRA+) cells coexpressed PRB. In the pubertal and adult virgin mammary gland, PRA+PRB+ cells also expressed nuclear cyclin D1 but did not contain the proliferation marker bromodeoxyuridine. Based on a lack of phosphorylated retinoblastoma protein expression and the expression patterns of the cyclin-dependent kinase inhibitors p21 and p27 in these cells, we conclude that PRA+PRB+ cells appear to be cell cycle arrested and do not proliferate. PRA+ cells were decreased in the adult gland and during and after pregnancy. The percentage of PRB+ cells was relatively constant throughout development, and in a significant proportion of cells, only PRB was detected. During development, and especially during pregnancy, a high percentage of PRB+ cells were positive for bromodeoxyuridine. From this observation, we conclude that these cells proliferate and that P acting through PRB may directly stimulate proliferation.

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 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
Sign in / Sign up

Export Citation Format

Share Document