Reference - Detail
| RRC ID | 51854 |
|---|---|
| Author | Yanagawa T, Denda K, Inatani T, Fukushima T, Tanaka T, Kumaki N, Inagaki Y, Komada M. |
| Title | Deficiency of X-Linked Protein Kinase Nrk during Pregnancy Triggers Breast Tumor in Mice. |
| Journal | Am J Pathol |
| Abstract |
The onset and/or growth of breast tumor are controlled, at least in part, by estrogen. Therefore, to prevent the development of breast tumor, estrogen-dependent proliferation of mammary epithelial cells during pregnancy needs to be suppressed once the mammary gland is fully developed to enable lactation. However, the underlying molecular mechanisms remain unknown. Nrk is an X-linked protein serine/threonine kinase in the germinal center kinase family. Herein, we demonstrate a frequent occurrence of breast tumors in homozygous and heterozygous Nrk mutant mice that have experienced pregnancy/parturition. The tumors never developed in the mutant mice without a history of pregnancy/parturition. They exhibited histopathological features of noninvasive tubular adenocarcinoma, and expressed estrogen receptor α. At late gestation when estrogen receptor α expression was significantly reduced in the wild-type mammary gland, grossly normal mammary glands in the pregnant Nrk mutant mice occasionally contained hyperplastic foci continuously expressing the receptor. Consistently, Nrk expression was induced in the wild-type mammary gland at this period of pregnancy. On the other hand, the pregnant Nrk mutant mice also showed elevated blood estrogen levels at late gestation. We suggest that Nrk suppresses the excessive proliferation of mammary epithelial cells during pregnancy, and the impairment of this regulatory system leads to frequent occurrence of breast tumor in Nrk mutant mice. |
| Volume | 186(10) |
| Pages | 2751-60 |
| Published | 2016-10-1 |
| DOI | 10.1016/j.ajpath.2016.06.005 |
| PII | S0002-9440(16)30228-0 |
| PMID | 27634343 |
| MeSH | Animals Breast / metabolism Breast / pathology Breast Neoplasms / enzymology* Breast Neoplasms / genetics Breast Neoplasms / pathology Down-Regulation Epithelial Cells / metabolism Epithelial Cells / pathology Estrogen Receptor alpha / genetics Estrogen Receptor alpha / metabolism Estrogens / blood Female Genes, X-Linked / genetics Germinal Center Kinases Humans Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Lactation MCF-7 Cells Male Mammary Neoplasms, Experimental / enzymology* Mammary Neoplasms, Experimental / genetics Mammary Neoplasms, Experimental / pathology Mice Mice, Transgenic Mutation Pregnancy Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism |
| IF | 3.491 |
| Times Cited | 5 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 25 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MCF7(RCB1904) |