title: APC +/- alters colonic fibroblast proteome in FAP.
abstract: 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.
authors.affiliation: Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Bhavinkumar B
authors.initials: BB
authors.lastname: Patel
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Li
authors.forename: Maketa P
authors.initials: MP
authors.lastname: Dixon
authors.forename: Elena L
authors.initials: EL
authors.lastname: Blagoi
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas
authors.forename: Steven H
authors.initials: SH
authors.lastname: Seeholzer
authors.forename: David
authors.initials: D
authors.lastname: Cheng
authors.forename: Yin A
authors.initials: YA
authors.lastname: He
authors.forename: Renata A
authors.initials: RA
authors.lastname: Coudry
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Howard
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Riddle
authors.forename: Harry C
authors.initials: HC
authors.lastname: Cooper
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Boman
authors.forename: Peggy
authors.initials: P
authors.lastname: Conrad
authors.forename: James A
authors.initials: JA
authors.lastname: Crowell
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellacosa
authors.forename: Alfred
authors.initials: A
authors.lastname: Knudson
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Yeung
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D020543:Proteome / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D020543:Proteome; D014157:Transcription Factors; C076224:RSU1 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1