scholarly journals Mammary Gland Development in Transgenic Male Mice Expressing Human P450 Aromatase

Endocrinology ◽  
2002 ◽  
Vol 143 (10) ◽  
pp. 4074-4083 ◽  
Author(s):  
Xiangdong Li ◽  
Anni Wärri ◽  
Sari Mäkelä ◽  
Tommi Ahonen ◽  
Tomi Streng ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Molecular Mechanisms ◽  
Mammary Gland Development ◽  
Hormone Receptors ◽  
Mammary Glands ◽  
Estrogen Receptor Α ◽  
Male Mice ◽  
Milk Protein Gene ◽  
Transgenic Mouse Strain ◽  
Gland Development

Abstract We recently generated a transgenic mouse strain that expresses the human aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown that in these mice the serum estradiol concentration is highly elevated, whereas the testosterone concentration is decreased. In the present study we examined mammary gland development in AROM+ male mice at different ages and found that the mammary glands of AROM+ males undergo ductal and alveolar development morphologically resembling that of terminally differentiated female mammary glands, expressing mRNA for a milk protein gene (β-casein). The male mammary glands also express multiple hormone receptors typical for female mammary gland: estrogen receptor α and β, progesterone receptor, and PRL receptor. Furthermore, data showed activation of the Stat5 (signal transducer and activator of transcription 5) signaling pathway in the AROM+ male mammary gland. Interestingly, the phenotype observed is in part reversible. Treatment with finrozole, a specific aromatase inhibitor, caused an involution of the differentiated phenotype of the mammary gland, marked by the disappearance of alveolar structures and the majority of the tertiary side branches of the ducts. The present animal model is a valuable tool for better understanding the cellular and molecular mechanisms involved in the development of gynecomastia.

Progesterone receptor membrane component 1 is required for mammary gland development†

2020 ◽  
Vol 103 (6) ◽  
pp. 1249-1259
Author(s):  
Globinna Kim ◽  
Jong Geol Lee ◽  
Seung-A Cheong ◽  
Jung-Min Yon ◽  
Myeong Sup Lee ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Mammary Gland Development ◽  
Target Genes ◽  
Hormone Treatment ◽  
Mammary Glands ◽  
Membrane Component ◽  
Independent Manner ◽  
Receptor Membrane ◽  
Gland Development

Abstract The physiological functions of progesterone (P4) in female reproductive organs including the mammary glands are mediated via the progesterone receptor (PR), but not all P4 functions can be explained by PR-mediated signaling. Progesterone receptor membrane component 1 (PGRMC1), a potential mediator of P4 actions, plays an important role in the ovary and uterus in maintaining female fertility and pregnancy, but its function in mammary glands has not been elucidated. This study investigated the role of PGRMC1 in mouse mammary gland development. Unlike in the uterus, exogenous estrogen (E2) and/or P4 did not alter PGRMC1 expression in the mammary gland, and Pgrmc1-knockout (KO) mice displayed reduced ductal elongation and side branching in response to hormone treatment. During pregnancy, PGRMC1 was expressed within both the luminal and basal epithelium and gradually increased with gestation and decreased rapidly after parturition. Moreover, although lactogenic capacity was normal after parturition, Pgrmc1 KO resulted in defective mammary gland development from puberty until midpregnancy, while the expression of PR and its target genes was not significantly different between wild-type and Pgrmc1-KO mammary gland. These data suggest that PGRMC1 is essential for mammary gland development during puberty and pregnancy in a PR-independent manner.

scholarly journals Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands

2003 ◽  
Vol 161 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Rui-An Wang ◽  
Ratna K. Vadlamudi ◽  
Rozita Bagheri-Yarmand ◽  
Iwan Beuvink ◽  
Nancy E. Hynes ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Ectopic Expression ◽  
Functional Differentiation ◽  
Mammary Glands ◽  
Pregnancy And Lactation ◽  
P21 Activated Kinase ◽  
Gland Development

Although growth factors have been shown to influence mammary gland development, the nature of downstream effectors remains elusive. In this study, we show that the expression of p21-activated kinase (Pak)1, a serine/threonine protein kinase, is activated in mammary glands during pregnancy and lactation. By targeting an ectopic expression of a kinase-dead Pak1 mutant under the control of ovine β-lactoglobulin promoter, we found that the mammary glands of female mice expressing kinase-dead Pak1 transgene revealed incomplete lobuloalveolar development and impaired functional differentiation. The expression of whey acidic protein and β-casein and the amount of activated Stat5 in the nuclei of epithelial cells in transgenic mice were drastically reduced. Further analysis of the underlying mechanisms revealed that Pak1 stimulated β-casein promoter activity in normal mouse mammary epithelial cells and also cooperated with Stat5a. Pak1 directly interacted with and phosphorylated Stat5a at Ser 779, and both COOH-terminal deletion containing Ser 779 of Stat5a and the Ser 779 to Ala mutation completely prevented the ability of Pak1 to stimulate β-casein promoter. Mammary glands expressing inactive Pak1 exhibited a reduction of Stat5a Ser 779 phosphorylation. These findings suggest that Pak1 is required for alveolar morphogenesis and lactation function, and thus, identify novel functions of Pak1 in the mammary gland development.

scholarly journals Signal Transducer and Activator of Transcription 5a Mediates Mammary Ductal Branching and Proliferation in the Nulliparous Mouse

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2876-2885 ◽  
Author(s):  
Sarah J. Santos ◽  
Sandra Z. Haslam ◽  
Susan E. Conrad
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Gland Development ◽  
Kinase Inhibitor ◽  
Mammary Epithelial Cells ◽  
Nuclear Factor Κb ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Signal Transducer ◽  
Gland Development

Signal transducer and activator of transcription (Stat)5a is a critical regulator of mammary gland development. Previous studies have focused on Stat5a’s role in the late pregnant and lactating gland, and although active Stat5a is detectable in mammary epithelial cells in virgin mice, little is known about its role during early mammary gland development. In this report, we compare mammary gland morphology in pubertal and adult nulliparous wild-type and Stat5a−/− mice. The Stat5a-null mammary glands exhibited defects in secondary and side branching, providing evidence that Stat5a regulates these processes. In addition, Stat5a−/− mammary glands displayed an attenuated proliferative response to pregnancy levels of estrogen plus progesterone (E+P), suggesting that it plays an important role in early pregnancy. Finally, we examined one potential mediator of Stat5a’s effects, receptor activator of nuclear factor-κB ligand (RANKL). Stat5a−/− mammary glands were defective in inducing RANKL in response to E+P treatment. In addition, regulation of several reported RANKL targets, including inhibitor of DNA binding 2 (Id2), cyclin D1, and the cyclin-dependent kinase inhibitor p21Waf1/Cip1, was altered in Stat5a−/− mammary cells, suggesting that one or more of these proteins mediate the effects of Stat5a in E+P-treated mammary epithelial cells.

The mammary gland development in male mice at nine weeks of age

1947 ◽  
Vol 97 (2) ◽  
pp. 223-237 ◽  
Author(s):  
Flavia L. Richardson ◽  
Arthur M. Cloudman
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Male Mice ◽  
Gland Development

scholarly journals An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

2020 ◽  
Author(s):  
Molly M. Wilson ◽  
Céline Callens ◽  
Matthieu Le Gallo ◽  
Svetlana Mironov ◽  
Qiong Ding ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Molecular Mechanisms ◽  
Mammary Gland Development ◽  
Epithelial Mesenchymal Transition ◽  
Gene Expression Signature ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Tumor Initiating Cells ◽  
Mesenchymal Transition ◽  
Gland Development

AbstractThe Epithelial–Mesenchymal Transition (EMT) and primary ciliogenesis induce stem cell properties in basal Mammary Stem Cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis at intermediate EMT transition states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote BBS11-dependent ubiquitination and inactivation of a central signaling node, GLIS2. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the Mammary-Tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC biology, mammary gland development, and claudin-low breast cancer formation.

scholarly journals Mammary Gland Development in Adult Mice Requires Epithelial and Stromal Estrogen Receptor α

Endocrinology ◽  
2002 ◽  
Vol 143 (6) ◽  
pp. 2357-2365 ◽  
Author(s):  
Stefan O. Mueller ◽  
James A. Clark ◽  
Page H. Myers ◽  
Kenneth S. Korach
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Estrogen Receptor Α ◽  
Adult Mice ◽  
Gland Development
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