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...

Descripción completa

Detalles Bibliográficos
Autores principales: Heijmans, Jarom, Muncan, Vanesa, Jacobs, Rutger J., de Jonge-Muller, Eveline S. M., Graven, Laura, Biemond, Izak, Ederveen, Antwan G., Groothuis, Patrick G., Mosselman, Sietse, Hardwick, James C., Hommes, Daniel W., van den Brink, Gijs R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144908/
https://www.ncbi.nlm.nih.gov/pubmed/21818351
http://dx.doi.org/10.1371/journal.pone.0022620
_version_ 1782209051662221312
author Heijmans, Jarom
Muncan, Vanesa
Jacobs, Rutger J.
de Jonge-Muller, Eveline S. M.
Graven, Laura
Biemond, Izak
Ederveen, Antwan G.
Groothuis, Patrick G.
Mosselman, Sietse
Hardwick, James C.
Hommes, Daniel W.
van den Brink, Gijs R.
author_facet Heijmans, Jarom
Muncan, Vanesa
Jacobs, Rutger J.
de Jonge-Muller, Eveline S. M.
Graven, Laura
Biemond, Izak
Ederveen, Antwan G.
Groothuis, Patrick G.
Mosselman, Sietse
Hardwick, James C.
Hommes, Daniel W.
van den Brink, Gijs R.
author_sort Heijmans, Jarom
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3144908
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31449082011-08-04 Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models Heijmans, Jarom Muncan, Vanesa Jacobs, Rutger J. de Jonge-Muller, Eveline S. M. Graven, Laura Biemond, Izak Ederveen, Antwan G. Groothuis, Patrick G. Mosselman, Sietse Hardwick, James C. Hommes, Daniel W. van den Brink, Gijs R. PLoS One Research Article 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. Public Library of Science 2011-07-27 /pmc/articles/PMC3144908/ /pubmed/21818351 http://dx.doi.org/10.1371/journal.pone.0022620 Text en Heijmans et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Heijmans, Jarom
Muncan, Vanesa
Jacobs, Rutger J.
de Jonge-Muller, Eveline S. M.
Graven, Laura
Biemond, Izak
Ederveen, Antwan G.
Groothuis, Patrick G.
Mosselman, Sietse
Hardwick, James C.
Hommes, Daniel W.
van den Brink, Gijs R.
Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title_full Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title_fullStr Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title_full_unstemmed Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title_short Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models
title_sort intestinal tumorigenesis is not affected by progesterone signaling in rodent models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144908/
https://www.ncbi.nlm.nih.gov/pubmed/21818351
http://dx.doi.org/10.1371/journal.pone.0022620
work_keys_str_mv AT heijmansjarom intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT muncanvanesa intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT jacobsrutgerj intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT dejongemullerevelinesm intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT gravenlaura intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT biemondizak intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT ederveenantwang intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT groothuispatrickg intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT mosselmansietse intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT hardwickjamesc intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT hommesdanielw intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels
AT vandenbrinkgijsr intestinaltumorigenesisisnotaffectedbyprogesteronesignalinginrodentmodels