Altered mammary gland development in the p53+/m mouse, a model of accelerated aging

被引：27

作者：

Gatza, Catherine E. ^{[1
,2
]}

Dumble, Melissa ^{[1
]}

Kittrell, Frances ^{[3
]}

Edwards, David G. ^{[3
]}

Dearth, Robert K. ^{[3
,4
]}

Lee, Adrian V. ^{[3
,4
]}

Xu, Jianming ^{[3
,4
]}

Medina, Daniel ^{[3
]}

Donehower, Lawrence A. ^{[1
,2
,3
]}

机构：

[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[2] Baylor Coll Med, Interdept Grad Program Cell & Mol Biol, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Med, Breast Ctr, Houston, TX 77030 USA

来源：

DEVELOPMENTAL BIOLOGY | 2008年 / 313卷 / 01期

关键词：

p53; mammary gland; mouse; ductal morphogenesis; IGF-1;

D O I：

10.1016/j.ydbio.2007.10.004

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The tumor suppressor p53 is important for inhibiting the development of breast carcinomas. However, little is known about the effects of increased p53 activity on mammary gland development. Therefore, the effect of p53 dosage on mammary gland development was examined by utilizing the p53+/m mouse, a p53 mutant which exhibits increased wild-type p53 activity, increased tumor resistance, a shortened longevity, and a variety of accelerated aging phenotypes. Here we report that p53+/m virgin mice exhibit a defect in mammary gland ductal morphogenesis. Transplants of mammary epithelium into p53+/m recipient mice demonstrate decreased outgrowth of wild-type and p53+/m donor epithelium, suggesting systemic or stromal alterations in the p53+/m mouse. Supporting these data, p53+/m mice display decreased levels of serum IGF-1 and reduced IGF-1 signaling in virgin glands. The induction of pregnancy or treatment of p53+m mice with estrogen, progesterone, estrogen and progesterone in combination, or IGF-1 stimulates ductal outgrowth, rescuing the p53+/m mammary phenotype. Serial mammary epithelium transplants demonstrate that p53+/m epithelium exhibits decreased transplant capabilities, suggesting early stem cell exhaustion. These data indicate that appropriate levels of p53 activity are important in regulating mammary gland ductal morphogenesis, in part through regulation of the IGF-1 pathway. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：130 / 141

页数：12

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