title: Changes in the expression of the peroxisome proliferator-activated receptor gamma gene in the colonic polyps and colonic mucosa of acromegalic patients.
abstract: Acromegalic patients have an increased prevalence of colonic neoplasms and lower peroxisome proliferator-activated receptor gamma (PPARgamma) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of PPARgamma in the biopsy samples of the polyps and outside polyps colonic mucosa from seven patients with active, untreated acromegaly, 11 with cured disease, and 15 controls. Serum GH and IGF-I levels were higher in patients with untreated acromegaly than in those with acromegaly in remission or controls (P = 0.003 and P = 0.002, respectively) The expression of PPARgamma mRNA (mean +/- SE) was 1) mucosa outside polyps, 24,188 +/- 3,254 transcripts in the controls, 22,432 +/- 2,006 transcripts in acromegaly in remission, and 1,952 +/- 342 transcripts in untreated acromegaly (P < 0.0001 vs. controls and acromegaly in remission); and 2) polyps mucosa, 1,554 +/- 236 transcripts in the controls, 1,112 +/- 143 in acromegaly in remission, and 1,570 +/- 251 in untreated acromegaly (P = NS among polyps groups and mucosa outside polyps of untreated acromegaly; P < 0.0001 vs. mucosa outside polyps of controls and acromegaly in remission). Eighty-five percent of the cells in the mucosa outside polyps from controls or acromegaly in remission were positive at immunohistochemistry, at variance with 45% of the cells from polyps mucosa from each group and from those of mucosa outside polyps of untreated acromegaly (P = 0.0002). In conclusion, patients with untreated acromegaly have reduced expression of PPARgamma in the mucosa outside polyps, which might be reversed by curing the disease; conversely, patients with acromegaly in remission have the same low levels of expression of PPARgamma in the polyps mucosa as untreated acromegaly or controls, supporting the concept that reduced expression of PPARgamma might be an early event in colonic tumorigenesis.
authors.affiliation: Department of Endocrinology, University of Pisa, 56124 Pisa, Italy. fbogazzi@hotmail.com
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
authors.forename: Federica
authors.initials: F
authors.lastname: Ultimieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Raggi
authors.forename: Dania
authors.initials: D
authors.lastname: Russo
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Denise
authors.initials: D
authors.lastname: Cecchetti
authors.forename: Aurelio
authors.initials: A
authors.lastname: Costa
authors.forename: Sandra
authors.initials: S
authors.lastname: Brogioni
authors.forename: Chiara
authors.initials: C
authors.lastname: Cosci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasperi
authors.forename: Luigi
authors.initials: L
authors.lastname: Bartalena
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
mesh_terms: D000172:Acromegaly / Q000378:metabolism*; D000328:Adult; D003106:Colon / Q000378:metabolism*; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism*; D003113:Colonoscopy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I