scholarly journals Δn89β-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland

2001 ◽  
Vol 153 (3) ◽  
pp. 555-568 ◽  
Author(s):  
Alexandra Imbert ◽  
Rachel Eelkema ◽  
Sara Jordan ◽  
Helen Feiner ◽  
Pamela Cowin
Keyword(s):  
Mammary Gland ◽  
Active Form ◽  
Mammary Glands ◽  
Downstream Effectors ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Development And Differentiation ◽  
Pregnant Mice ◽  
Ductal Branching

To investigate the role of β-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of β-catenin lacking the NH2-terminal 89 amino acids (ΔN89β-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that ΔN89β-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin ΔN89β-catenin mammary glands resemble those found in wild-type (wt) pregnant mice and inappropriately express cyclin D1 mRNA. In contrast to wt mammary glands, which resume a virgin appearance after cessation of lactation, transgenic mammary glands involute to a midpregnant status. All transgenic females develop multiple aggressive adenocarcinomas early in life. Surprisingly, the ΔN89β-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, ΔN89β-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.

scholarly journals A Novel Mechanism of Resistance to Mouse Mammary Tumor Virus Infection

2000 ◽  
Vol 74 (6) ◽  
pp. 2752-2759 ◽  
Author(s):  
Tatyana V. Golovkina
Keyword(s):  
Mammary Gland ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Inbred Mice ◽  
Tumor Development ◽  
Mammary Glands ◽  
Mammary Tissue ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Exogenous mouse mammary tumor virus (MMTV) is carried from the gut of suckling pups to the mammary glands by lymphocytes and induces mammary gland tumors. MMTV-induced tumor incidence in inbred mice of different strains ranges from 0 to as high as 100%. For example, mice of the C3H/HeN strain are highly susceptible, whereas mice of the I/LnJ strain are highly resistant. Of the different factors that together determine the susceptibility of mice to development of MMTV-induced mammary tumors, genetic elements play a major role, although very few genes that determine a susceptibility-resistance phenotype have been identified so far. Our data indicate that MMTV fails to infect mammary glands in I/LnJ mice foster nursed on viremic C3H/HeN females, even though the I/LnJ mammary tissue is not refractory to MMTV infection. Lymphocytes from fostered I/LnJ mice contained integrated MMTV proviruses and shed virus but failed to establish infection in the mammary glands of susceptible syngeneic (I × C3H.JK)F1 females. Based on the susceptible-resistant phenotype distribution in N2 females, both MMTV mammary gland infection and mammary gland tumor development in I/LnJ mice are controlled by a single locus.

scholarly journals Role of F-Box Protein βTrcp1 in Mammary Gland Development and Tumorigenesis

2004 ◽  
Vol 24 (18) ◽  
pp. 8184-8194 ◽  
Author(s):  
Yasusei Kudo ◽  
Daniele Guardavaccaro ◽  
Patricia G. Santamaria ◽  
Ryo Koyama-Nasu ◽  
Esther Latres ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transgenic Mice ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Ductal Branching ◽  
F Box Protein ◽  
Gland Development

ABSTRACT The F-box protein βTrcp1 controls the stability of several crucial regulators of proliferation and apoptosis, including certain inhibitors of the NF-κB family of transcription factors. Here we show that mammary glands of βTrcp1−/− female mice display a hypoplastic phenotype, whereas no effects on cell proliferation are observed in other somatic cells. To investigate further the role of βTrcp1 in mammary gland development, we generated transgenic mice expressing human βTrcp1 targeted to epithelial cells under the control of the mouse mammary tumor virus (MMTV) long terminal repeat promoter. Compared to controls, MMTV βTrcp1 mammary glands display an increase in lateral ductal branching and extensive arrays of alveolus-like protuberances. The mammary epithelia of MMTV βTrcp1 mice proliferate more and show increased NF-κB DNA binding activity and higher levels of nuclear NF-κB p65/RelA. In addition, 38% of transgenic mice develop tumors, including mammary, ovarian, and uterine carcinomas. The targeting of βTrcp1 to lymphoid organs produces no effects on these tissues. In summary, our results support the notion that βTrcp1 positively controls the proliferation of breast epithelium and indicate that alteration of βTrcp1 function and expression may contribute to malignant behavior of breast tumors, at least in part through NF-κB transactivation.

An entire functional mammary gland may comprise the progeny from a single cell

Development ◽  
1998 ◽  
Vol 125 (10) ◽  
pp. 1921-1930 ◽  
Author(s):  
E.C. Kordon ◽  
G.H. Smith
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Mammary Epithelial ◽  
Self Renewal ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional gland when transplanted into an epithelium-free mammary fat pad. Mouse mammary hyperplasias and tumors are clonal dominant populations and probably represent the progeny of a single transformed cell. Our study provides evidence that single multipotent stem cells positioned throughout the mature fully developed mammary gland have the capacity to produce sufficient differentiated progeny to recapitulate an entire functional gland. Our evidence also demonstrates that these stem cells are self-renewing and are found with undiminished capacities in the newly regenerated gland. We have taken advantage of an experimental model where mouse mammary tumor virus infects mammary epithelial cells and inserts a deoxyribonucleic acid copy(ies) of its genome during replication. The insertions occur randomly within the somatic genome. CzechII mice have no endogenous nucleic acid sequence homology with mouse mammary tumor virus; therefore all viral insertions may be detected by Southern analysis provided a sufficient number of cells contain a specific insertional event. Transplantation of random fragments of infected CzechII mammary gland produced clonal-dominant epithelial populations in epithelium-free mammary fat pads. Serial transplantation of pieces of the clonally derived outgrowths produced second generation glands possessing the same viral insertion sites providing evidence for self-renewal of the original stem cell. Limiting dilution studies with cell cultures derived from third generation clonal outgrowths demonstrated that three multipotent but distinct mammary epithelial progenitors were present in clonally derived mammary epithelial populations. Estimation of the potential number of multipotent epithelial cells that may be evolved from an individual mammary-specific stem cell by self-renewal is in the order of 10(12)-10(13). Therefore, one stem cell might easily account for the renewal of mammary epithelium over several transplant generations.

Effect of pregestational sialoadenectomy of nursing mothers on eyelid opening of pups

1985 ◽  
Vol 249 (3) ◽  
pp. R285-R289
Author(s):  
S. Okamoto ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Submandibular Gland ◽  
Mammary Glands ◽  
Submandibular Glands ◽  
Nursing Mothers ◽  
Pregnant Mice ◽  
Epidermal Growth

The eyelid opening of pups born to and nursed by normal mice occurred by the 15th day of birth, whereas pregestational sialoadenectomy (removal of submandibular glands) of nursing mice delayed eyelid opening of their pups by as much as 5 days. Parotidectomy, however, had no effect on eyelid opening. Cross-foster nursing experiments indicated that the cause for delayed eyelid opening of pups was to be found in sialoadenectomized mothers, not their pups. Sialoadenectomized mothers had underdeveloped mammary glands that produced approximately 50% less milk than controls, and the amount of epidermal growth factor in their milk was similarly reduced. When epidermal growth factor, a polypeptide produced by the submandibular gland, was injected daily at a dose of 5 micrograms into sialoadenectomized pregnant mice, the eyelid opening of the pups nursed by their mothers occurred normally. These results are discussed with regard to the possible role of the submandibular gland and epidermal growth factor in neonatal eyelid opening.

The inflammatory environment mediated by a high-fat diet inhibited the development of mammary glands and destroyed the tight junction in pregnant mice.

2020 ◽  
Vol 11 (9) ◽  
pp. 8193-8201
Author(s):  
Wenjin Guo ◽  
Juxiong Liu ◽  
Shuang Hou ◽  
Guiqiu Hu ◽  
He Ma ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Tight Junction ◽  
Pregnant Women ◽  
High Fat Diet ◽  
Mammary Glands ◽  
High Fat ◽  
Pregnant Mice

Long-term intake of a high-fat diet seriously affects the health of pregnant women and leads to increased levels of inflammation in the mammary gland.

scholarly journals CDP Binding to Multiple Sites in the Mouse Mammary Tumor Virus Long Terminal Repeat Suppresses Basal and Glucocorticoid-Induced Transcription

2002 ◽  
Vol 76 (5) ◽  
pp. 2168-2179 ◽  
Author(s):  
Quan Zhu ◽  
Jaquelin P. Dudley
Keyword(s):  
Mammary Gland ◽  
Reporter Gene ◽  
Binding Sites ◽  
Mouse Mammary Tumor Virus ◽  
Mammary Gland Development ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Mmtv Ltr ◽  
Gland Development

ABSTRACT Mouse mammary tumor virus (MMTV) is transcribed at high levels in the lactating mammary gland to ensure transmission of virus from the milk of infected female mice to susceptible offspring. We previously have shown that the transcription factor CCAAT displacement protein (CDP) is expressed in high amounts in virgin mammary gland, yet DNA-binding activity for the MMTV long terminal repeat (LTR) disappears as mammary tissue differentiates during lactation. CDP is a repressor of MMTV expression and, therefore, MMTV expression is suppressed during early mammary gland development. In this study, we have shown using DNase I footprinting and electrophoretic mobility shift assays that there are at least five CDP-binding sites in the MMTV LTR upstream of those previously described in the promoter-proximal negative regulatory element (NRE). Single mutations in two of these upstream sites (+691 or +692 and +735 relative to the first base of the LTR) reduced CDP binding to the cognate sites and elevated reporter gene expression from the full-length MMTV LTR. Combination of a mutation in the promoter-distal NRE with a mutation in the proximal NRE gave approximately additive increases in LTR-reporter gene activity, suggesting that these binding sites act independently. Mutations in several different CDP-binding sites allowed elevation of reporter gene activity from the MMTV promoter in the absence and presence of glucocorticoids, hormones that contribute to high levels of MMTV transcription during lactation by activation of hormone receptor binding to the LTR. In addition, overexpression of CDP in transient-transfection assays suppressed both basal and glucocorticoid-induced LTR-mediated transcription in a dose-dependent manner. These data suggest that multiple CDP-binding sites contribute independently to regulate binding of positive factors, including glucocorticoid receptor, to the MMTV LTR during mammary gland development.

scholarly journals The differential actions of cortisol on the synthesis and turnover of alpha-lactalbumin and casein and on accumulation of their mRNA in mouse mammary gland in organ culture

1983 ◽  
Vol 212 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Y Nagamatsu ◽  
T Oka
Keyword(s):  
Mammary Gland ◽  
Marked Decrease ◽  
Milk Proteins ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Marked Enhancement ◽  
Pregnant Mice ◽  
Translatable Mrna ◽  
Casein Synthesis ◽  
Alpha Lactalbumin

Cortisol was previously shown to exert different, concentration-dependent, effects on the accumulation of casein and alpha-lactalbumin in mammary glands from mid-pregnant mice cultured in the presence of insulin and prolactin [Ono & Oka (1980) Cell 19, 473-480]. The present study demonstrated that the addition of 30nM-cortisol to the medium containing insulin and prolactin resulted in a marked enhancement of the rate of synthesis of both alpha-lactalbumin and casein in cultured tissue. The addition of 3 microM-cortisol in combination with insulin and prolactin caused a marked decrease in the rate of alpha-lactalbumin synthesis, but increased casein synthesis substantially. Similar changes were also observed in the amount of translatable mRNA for alpha-lactalbumin and casein in mammary explants cultured with insulin, prolactin and the two concentrations of cortisol. The study of the turnover of the milk proteins in cultured explants showed that virtually all of the casein synthesized remained intact in tissue explants cultured with 3 microM cortisol, whereas about 45% of casein disappeared in 40h from explants cultured with 30nM-cortisol. In contrast, the two concentrations of cortisol did not differentially affect the disappearance of alpha-lactalbumin, which was about 55% in 40h. These results indicate that the concentration-dependent differential actions of cortisol on the accumulation of alpha-lactalbumin and casein are exerted through its effects on the rate of synthesis and turnover of the two proteins as well as on the accumulation of their mRNA species.

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