Pubertal Mammary Gland Development: Elucidation of In Vivo Morphogenesis Using Murine Models

2016 ◽  
pp. 77-114 ◽  
Author(s):  
Jean McBryan ◽  
Jillian Howlin
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Murine Models ◽  
Gland Development

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 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.

Wnt-responsive element controls Lef-1 promoter expression during submucosal gland morphogenesis

2004 ◽  
Vol 287 (4) ◽  
pp. L752-L763 ◽  
Author(s):  
Ryan R. Driskell ◽  
Xiaoming Liu ◽  
Meihui Luo ◽  
Mohammed Filali ◽  
Weihong Zhou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transcriptional Control ◽  
Mammary Gland Development ◽  
Expression Patterns ◽  
Developmental Expression ◽  
Submucosal Gland ◽  
Bud Formation ◽  
Responsive Element ◽  
Gland Development

Regulated expression of lymphoid enhancer factor 1 (Lef-1) plays an obligatory role in the transcriptional control of epithelial bud formation during airway submucosal gland and mammary gland development. However, regions of the Lef-1 promoter required for spatial and temporal regulation during glandular development have yet to be defined. We hypothesized that a previously reported 110-bp Wnt-responsive element (WRE) in the Lef-1 promoter, which can be induced by Wnt-3a/β-catenin signals, may also play a role in regulating Lef-1 expression during airway and mammary gland development. Here we show that the Lef-1 promoter is also responsive to Wnt-1 signals in both airway and mammary epithelial cell lines. To better understand the importance of the WRE in dynamically regulating Lef-1 promoter activation in these two types of epithelia in vivo, we utilized LacZ reporter transgenic mice to evaluate the significance of Wnt-responsive sequences in the Lef-1 promoter during glandular bud formation. A 2.5-kb Lef-1 promoter fragment partially reproduced endogenous Lef-1 expression patterns in a subset of cell types involved in both mammary gland and submucosal glandular bud development. Interestingly, removal of the 110-bp WRE from the Lef-1 promoter ablated expression in nasal and tracheal submucosal glandular buds while having no significant effect on developmental expression in mammary glandular buds. These findings suggest that Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation.

scholarly journals Banana Peels (Musa paradisiaca L.) Extract as Phytoestrogen on Ovariectomized Mice Mammary Gland Development by Inducing c-Myc Expression

2011 ◽  
Vol 2 (1) ◽  
pp. 151
Author(s):  
Nanda Resa Pratama ◽  
Yurista Gilang ◽  
Rita Riata ◽  
Adam Hermawan ◽  
Muthi' Ikawati ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Molecular Docking ◽  
Mammary Gland ◽  
In Silico ◽  
Mammary Gland Development ◽  
Ovariectomized Rats ◽  
Banana Peel ◽  
Base Line ◽  
Gland Development

Hormone Replacement Therapy (HRT) is therapy for estrogen deficiency and post menopausal syndromes, but high cost and unwell-secured therapy. One of alternative therapy is the usage of phytoestrogens. The banana peel contains flavones, flavonol, flavanone and polimethoxyflavone which are potential as phytoestrogen. The purpose of this study was to examine the estrogenic effect of banana peel extract (BPE) development of mammary gland of ovariectomized rats. Estrogenic effects was examined based on in vivo and in silico experiment. For in vivo experiment, female Sprague-dawley rats aged 50 days were ovariectomized. At 70 days of age, 12 rats were treated with BPE 500 mg/kgBB and 1000mg/kgBB, 5 rats were treated with estradiol 2μg/day while others served as control were treated with CMC-Na 0.5% and sacrificed 2 weeks later. The base line ovariectomized rats and base line non-ovariectomized rats were sacrificed at 70 days of age. The in silico experiment examined by molecular docking between myricetin and estrogen receptor alpha (ER-α). The result of in vivo experiment showed that 1000 mg/kgBW BPE induced c-Myc expression and enhance ovariectomized rat mammary gland development significantly. Meanwhile, molecular docking showed that there are hydrogen bond interaction between bioactive compound in BPE and Estrogen Receptor (ER)-α but less powerfull than estrogen and ER-α interaction. In summary, BPE can act as an estrogen agonist, resulting in the enhancement of c-Myc expression.Keywords: banana peels extract (BPE), phytoestrogen, mammary gland, ovariectomized rats

Epithelial cell cycling predicts p53 responsiveness to γ-irradiation during post-natal mammary gland development

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2997-3008
Author(s):  
Lisa M. Minter ◽  
Ellen S. Dickinson ◽  
Stephen P. Naber ◽  
D. Joseph Jerry
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Steroid Hormones ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Γ Irradiation ◽  
Radiation Induced ◽  
Gland Development

The tumor suppressor gene, TP53, plays a major role in surveillance and repair of radiation-induced DNA damage. In multiple cell types, including mammary epithelial cells, abrogation of p53 (encoded by Trp53) function is associated with increased tumorigenesis. We examined γ-irradiated BALB/c-Trp53+/+ and -Trp53–/– female mice at five stages of post-natal mammary gland development to determine whether radiation-induced p53 activity is developmentally regulated. Our results show that p53-mediated responses are attenuated in glands from irradiated virgin and lactating mice, as measured by induction of p21/WAF1 (encoded by Cdkn1a) and apoptosis, while irradiated early- and mid-pregnancy glands exhibit robust p53 activity. There is a strong correlation between p53-mediated apoptosis and the degree of cellular proliferation, independent of the level of differentiation. In vivo, proliferation is intimately influenced by steroid hormones. To determine whether steroid hormones directly modulate p53 activity, whole organ cultures of mammary glands were induced to proliferate using estrogen plus progesterone or epidermal growth factor plus transforming growth factor-α and p53 responses to γ-irradiation were measured. Regardless of mitogens used, proliferating mammary epithelial cells show comparable p53 responses to γ-irradiation, including expression of nuclear p53 and p21/WAF1 and increased levels of apoptosis, compared to non-proliferating irradiated control cultures. Our study suggests that differences in radiation-induced p53 activity during post-natal mammary gland development are influenced by the proliferative state of the gland, and may be mediated indirectly by the mitogenic actions of steroid hormones in vivo.

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 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.

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