APC+/− alters colonic fibroblast proteome in FAP

Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation ca...

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Main Authors:	Patel, Bhavinkumar B., Li, Xin-Ming, Dixon, Maketa P., Blagoi, Elena L., Nicolas, Emmanuelle, Seeholzer, Steven H., Cheng, David, He, Yin A., Coudry, Renata A., Howard, Sharon D., Riddle, Dawn M., Cooper, Harry S., Boman, Bruce M., Conrad, Peggy, Crowell, James A., Bellacosa, Alfonso, Knudson, Alfred, Yeung, Anthony T., Kopelovich, Levy
Format:	Online
Language:	English
Published:	Impact Journals LLC 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195363/

id	pubmed-3195363
recordtype	oai_dc
spelling	pubmed-31953632011-10-17 APC+/− alters colonic fibroblast proteome in FAP Patel, Bhavinkumar B. Li, Xin-Ming Dixon, Maketa P. Blagoi, Elena L. Nicolas, Emmanuelle Seeholzer, Steven H. Cheng, David He, Yin A. Coudry, Renata A. Howard, Sharon D. Riddle, Dawn M. Cooper, Harry S. Boman, Bruce M. Conrad, Peggy Crowell, James A. Bellacosa, Alfonso Knudson, Alfred Yeung, Anthony T. Kopelovich, Levy Research Papers Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01). More than 4,000 protein spots were quantified by 2D PAGE analysis, identifying 368 non-redundant proteins and 400 of their isoforms. Specifically, all three classes of cytoskeletal filaments and their regulatory proteins were altered as were oxidative stress response proteins. Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers. The results indicate that heterozygosity for a mutant APC tumor suppressor gene alters the proteomes of both colon-derived normal fibroblasts in a gene-specific manner, consistent with a “one-hit” effect. Impact Journals LLC 2011-03-15 /pmc/articles/PMC3195363/ /pubmed/21411865 Text en Copyright: © 2011 Patel et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Patel, Bhavinkumar B. Li, Xin-Ming Dixon, Maketa P. Blagoi, Elena L. Nicolas, Emmanuelle Seeholzer, Steven H. Cheng, David He, Yin A. Coudry, Renata A. Howard, Sharon D. Riddle, Dawn M. Cooper, Harry S. Boman, Bruce M. Conrad, Peggy Crowell, James A. Bellacosa, Alfonso Knudson, Alfred Yeung, Anthony T. Kopelovich, Levy
spellingShingle	Patel, Bhavinkumar B. Li, Xin-Ming Dixon, Maketa P. Blagoi, Elena L. Nicolas, Emmanuelle Seeholzer, Steven H. Cheng, David He, Yin A. Coudry, Renata A. Howard, Sharon D. Riddle, Dawn M. Cooper, Harry S. Boman, Bruce M. Conrad, Peggy Crowell, James A. Bellacosa, Alfonso Knudson, Alfred Yeung, Anthony T. Kopelovich, Levy APC+/− alters colonic fibroblast proteome in FAP
author_facet	Patel, Bhavinkumar B. Li, Xin-Ming Dixon, Maketa P. Blagoi, Elena L. Nicolas, Emmanuelle Seeholzer, Steven H. Cheng, David He, Yin A. Coudry, Renata A. Howard, Sharon D. Riddle, Dawn M. Cooper, Harry S. Boman, Bruce M. Conrad, Peggy Crowell, James A. Bellacosa, Alfonso Knudson, Alfred Yeung, Anthony T. Kopelovich, Levy
author_sort	Patel, Bhavinkumar B.
title	APC+/− alters colonic fibroblast proteome in FAP
title_short	APC+/− alters colonic fibroblast proteome in FAP
title_full	APC+/− alters colonic fibroblast proteome in FAP
title_fullStr	APC+/− alters colonic fibroblast proteome in FAP
title_full_unstemmed	APC+/− alters colonic fibroblast proteome in FAP
title_sort	apc+/− alters colonic fibroblast proteome in fap
description	Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01). More than 4,000 protein spots were quantified by 2D PAGE analysis, identifying 368 non-redundant proteins and 400 of their isoforms. Specifically, all three classes of cytoskeletal filaments and their regulatory proteins were altered as were oxidative stress response proteins. Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers. The results indicate that heterozygosity for a mutant APC tumor suppressor gene alters the proteomes of both colon-derived normal fibroblasts in a gene-specific manner, consistent with a “one-hit” effect.
publisher	Impact Journals LLC
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195363/
_version_	1611481662949949440

APC+/− alters colonic fibroblast proteome in FAP

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