Apoptosis is reduced in the colonic mucosa of patients with acromegaly.
BACKGROUND
Patients with acromegaly have an increased risk of developing colonic tumours; reduced apoptosis is considered a leading mechanism in tumorigenesis. GH and IGF-1 decrease apoptosis in several cell lines including human colonic adenocarcinoma, but it is unknown whether epithelial cells of colonic mucosa of patients with acromegaly have reduced apoptosis.


OBJECTIVE
The aim of the study was to evaluate the degree of apoptosis in a cross-sectional study, in biopsy samples of colonic mucosa obtained from patients with acromegaly.


METHODS
Eleven patients with active, untreated acromegaly (AcroUntr), 16 patients with acromegaly in remission (AcroRem) and 23 controls were enrolled in the study. Samples of colonic mucosa were obtained during colonoscopy; apoptosis was evaluated by either DNA fragmentation or terminal deoxynucleotidyl transferase assay.


RESULTS
Apoptotic cells were 60.0 +/- 2.5% in samples of colonic mucosa of controls, 62.0 +/- 3.4% in those from patients with AcroRem (P = ns vs. controls), and 39.0 +/- 4.1% in those from patients with AcroUntr (P < 0.0001 vs. the other groups). Apoptosis was inversely related to serum IGF-I (r = 0.771, P < 0.001) or GH (r = 0.404, P = 0.05) levels and less to the estimated duration of disease (r = 0.384, P = 0.07). PPARgamma is considered to be a tumour suppressor gene the expression of which might be involved in colonic tumorigenesis. The expression of PPARgamma was lower in the colonic mucosa of patients with AcroUntr (2845 +/- 947 transcripts) than in that of controls (35 200 +/- 2450 transcripts) or AcroRem (29 547 +/- 3650 transcripts) (P < 0.005). The recovery of PPARgamma expression was associated with apoptosis in most cells. The lower degree of apoptosis in patients with AcroUntr was associated with a reduced expression of the antiapoptotic Bax protein.


CONCLUSIONS
In conclusion, patients with AcroUntr have reduced apoptosis in colonic mucosa that is apparently reversed after acromegaly is cured. It is conceivable that reduced apoptosis may represent an early event in colonic tumorigenesis of patients with acromegaly.
Bogazzi
Fausto
F
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. f.bogazzi@endoc.med.unipi.it
Russo
Dania
D
Locci
Maria Teresa
MT
Chifenti
Barbara
B
Ultimieri
Federica
F
Raggi
Francesco
F
Cosci
Chiara
C
Sardella
Chiara
C
Costa
Aurelio
A
Gasperi
Maurizio
M
Bartalena
Luigi
L
Martino
Enio
E
D000172:Acromegaly / Q000097:blood / Q000473:pathology*; D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D003106:Colon; D003113:Colonoscopy; D003430:Cross-Sectional Studies; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007413:Intestinal Mucosa / Q000473:pathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047495:PPAR gamma; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone