Intestinal tumorigenesis is not affected by progesterone signaling in rodent models
Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the proge...
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Published in | PloS one Vol. 6; no. 7; p. e22620 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
27.07.2011
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the Apc(Min/+) mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+) mice exhibited no change in polyp number, size or localization compared to Apc(Min/+). To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis. |
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Bibliography: | Conceived and designed the experiments: JH VM GRvdB. Performed the experiments: JH VM RJJ ESMJ-M LG. Analyzed the data: JH VM RJJ LG. Wrote the paper: JH GRvdB. Set up mouse breeding: IB. Discussed data, critically read and discussed the manuscript: AGE PG SM JCH DWH. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0022620 |