title: Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands. j.heijmans@amc.nl
authors.forename: Jarom
authors.initials: J
authors.lastname: Heijmans
authors.forename: Vanesa
authors.initials: V
authors.lastname: Muncan
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Jacobs
authors.forename: Eveline S M
authors.initials: ES
authors.lastname: de Jonge-Muller
authors.forename: Laura
authors.initials: L
authors.lastname: Graven
authors.forename: Izak
authors.initials: I
authors.lastname: Biemond
authors.forename: Antwan G
authors.initials: AG
authors.lastname: Ederveen
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Groothuis
authors.forename: Sietse
authors.initials: S
authors.lastname: Mosselman
authors.forename: James C
authors.initials: JC
authors.lastname: Hardwick
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.forename: Gijs R
authors.initials: GR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D044483:Intestinal Polyposis / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000494:pharmacology; D051381:Rats; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone