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.

scholarly journals p19ARFDetermines the Balance between Normal Cell Proliferation Rate and Apoptosis during Mammary Gland Development

2004 ◽  
Vol 15 (5) ◽  
pp. 2302-2311 ◽  
Author(s):  
Yijun Yi ◽  
Anne Shepard ◽  
Frances Kittrell ◽  
Biserka Mulac-Jericevic ◽  
Daniel Medina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Protein Level ◽  
Normal Cell ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Proliferation Rate ◽  
Gland Development

This study demonstrated, for the first time, the following events related to p19ARFinvolvement in mammary gland development: 1) Progesterone appears to regulate p19ARFin normal mammary gland during pregnancy. 2) p19ARFexpression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19ARFprotein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19ARFin mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulation of p21Cip1and decrease in apoptosis, and 2) p19ARFnull cells are immortal in vivo measured by serial transplantion, which is partly attributed to complete absence of p21Cip1compared with WT cells. Although, p19ARFis dispensable in mammary alveologenesis, as evidenced by normal differentiation in the mammary gland of pregnant p19ARFnull mice, the upregulation of p19ARFby progesterone in the WT cells and the weakness of p21Cip1in mammary epithelial cells lacking p19ARFstrongly suggest that the functional role(s) of p19ARFin mammary gland development is critical to sustain normal cell proliferation rate during pregnancy and normal apoptosis in involution possibly through the p53-dependent pathway.

scholarly journals Survival and Differentiation of Mammary Epithelial Cells in Mammary Gland Development Require Nuclear Retention of Id2 Due to RANK Signaling

2011 ◽  
Vol 31 (23) ◽  
pp. 4775-4788 ◽  
Author(s):  
N.-S. Kim ◽  
H.-T. Kim ◽  
M.-C. Kwon ◽  
S.-W. Choi ◽  
Y.-Y. Kim ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Nuclear Retention ◽  
Rank Signaling ◽  
Gland Development

scholarly journals Expression of an engrailed-LMO4 fusion protein in mammary epithelial cells inhibits mammary gland development in mice

Oncogene ◽  
2003 ◽  
Vol 23 (8) ◽  
pp. 1507-1513 ◽  
Author(s):  
Ning Wang ◽  
Elena Kudryavtseva ◽  
Irene L Ch'en ◽  
Joshua McCormick ◽  
Tod M Sugihara ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Fusion Protein ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Gland Development

The Biology of Zinc Transport in Mammary Epithelial Cells: Implications for Mammary Gland Development, Lactation, and Involution

2013 ◽  
Vol 19 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Nicholas H. McCormick ◽  
Stephen R. Hennigar ◽  
Kirill Kiselyov ◽  
Shannon L. Kelleher
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Zinc Transport ◽  
Gland Development

scholarly journals Circ-140/chi-miR-8516/STC1-MMP1 Regulates αs1-/β-Casein Secretion and Lipid Formation in Goat Mammary Epithelial Cells

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 671
Author(s):  
Yue Zhang ◽  
Qiong Wu ◽  
Jidan Liu ◽  
Xiaopeng An ◽  
Binyun Cao
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Essential Role ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Lipid Formation ◽  
Milk Components ◽  
Gland Development ◽  
Goat Mammary Epithelial Cells

MicroRNAs play an essential role in mammary gland development, and involution is a factor that limits lactation. Chi-miR-8516 is one of the validated microRNAs that regulates the expression of STC1 and MMP1, which surge during the involution of the mammary gland. This study aims to explore the direct or indirect regulation of STC1 and MMP1 by chi-miR-8516 and the regulation of chi-miR-8516 by circ-140. In goat mammary epithelial cells, we found that chi-miR-8516 takes circ-140 as a sponge and regulates MMP1 expression by targeting STC1 and promoting the phosphorylation of MAPK. The examination of αs1-/β-casein and lipid showed the modulation of the circ-140/chi-miR-8516/STC1-MMP1 axis in casein secretion and lipid formation, which was regulated by the phosphorylation of mTOR and STAT5. This study illustrates an axis that regulates the synthesis of milk components, and explores the pathways in which the axis participates.

Wheat gluten during pregnancy and lactation: effects on mammary gland development and pup viability

1987 ◽  
Vol 46 (2) ◽  
pp. 250-257 ◽  
Author(s):  
G R Jansen ◽  
C Grayson ◽  
H Hunsaker
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Wheat Gluten ◽  
Pregnancy And Lactation ◽  
Gland Development

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 Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution

2003 ◽  
Vol 177 (2) ◽  
pp. 305-317 ◽  
Author(s):  
D Schams ◽  
S Kohlenberg ◽  
W Amselgruber ◽  
B Berisha ◽  
MW Pfaffl ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Western Blotting ◽  
Mammary Gland Development ◽  
Mammary Tissue ◽  
Positive Staining ◽  
Bovine Mammary Gland ◽  
Total Rna ◽  
Gland Development

It is now well established that oestrogen and progesterone are absolutely essential for mammary gland development. Lactation can be induced in non-pregnant animals by sex steroid hormone treatment. Most of the genomic actions of oestrogens are mediated by two oestrogen receptors (ER)-alpha and ERbeta, and for gestagens in ruminants by the progesterone receptor (PR). Our aim was the evaluation of mRNA expression and protein (localisation and Western blotting) during mammogenesis, lactogenesis, galactopoiesis (early, middle and late) and involution (8, 24, 28, 96-108 h and 14-28 days after the end of milking) in the bovine mammary gland (total no. 53). During these stages, the mRNA was assessed by means of real-time RT-PCR (LightCycler). The protein for ERalpha, ERbeta and PR was localised by immunohistochemistry and Western blotting. The mRNA expression results indicated the existence of ERalpha, ERbeta and PR in bovine mammary gland. Both ERalpha and PR are expressed in fg/ micro g total RNA range. The highest mRNA expression was found for ERalpha and PR in the tIssue of non-pregnant heifers, followed by a significant decrease to a lower level at the time of lactogenesis with low concentrations remaining during lactation and the first 4 weeks of involution. In contrast, the expression of ERbeta was about 1000-fold lower (ag/ micro g total RNA) and showed no clear difference during the stages examined, with a significant increase only 2-4 weeks after the end of milking. Immunolocalisation for ERalpha revealed a strong positive staining in nuclei of lactocytes in non-pregnant heifers, became undetectable during pregnancy, lactogenesis and lactation, and was again detectable 14-28 days after the end of milking. In contrast, PR was localised in the nuclei of epithelial cells in the mammary tIssue of non-pregnant heifers, in primigravid animals, and during late lactation and involution. During lactogenesis, peak and mid lactation, fewer nuclei of epithelial cells were positive, but increased staining of the cytoplasm of epithelial cells was obvious. ERalpha and ERbeta protein was found in all mammary gland stages examined by Western blotting. In contrast to mRNA expression, the protein signal for ERalpha was weaker in the tIssue of non-pregnant heifers and during involution (4 weeks). ERbeta protein showed a stronger signal (two isoform bands) in non-pregnant heifers and 4 weeks after the end of milking. This correlated with the mRNA expression data. Three isoforms of PR (A, B and C) were found by Western blotting in the tIssue of non-pregnant heifers, but only isoform B remained during the following stages (lactogenesis, galactopoiesis and involution). In conclusion, the mRNA expression and protein data for ER and PR showed clear regulatory changes, suggesting involvement of these receptors in bovine mammary gland development and involution.

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