Decreased levels of precursor transforming growth factor beta1 in human colorectal cancer.
Transforming growth factor (TGF) beta1 is a growth factor with wide-ranging effects on proliferation, differentiation, immunosuppression, apoptosis and matrix remodelling. TGFbeta1 seems to have an antitumorigenic role in the gastrointestinal tract but may also be associated with the development of colorectal cancer. Initially, TGFbeta1 is produced in a latent (precursor) form in epithelial cells and then is activated by a not clearly understood multistep process. In this study, we analysed precursor TGFbeta1 protein expression (n=40) and TGFbeta1 gene expression (n=49) in human colorectal adenocarcinomas and 49 normal adjacent tissue. Out of these 49 normal tissues 40 were matched. Western blot analysis revealed that the precursor TGFbeta1 protein levels were generally lower in colorectal cancerous tissue compared to adjacent non-cancerous tissue (P<0.001). Furthermore, with real-time PCR our results cannot reflect a statistically significant difference in TGFbeta1 gene expression between the tumour tissue and normal tissue. These finds indicate that it is likely that there are mechanisms which control precursor TGFbeta1 protein expression by factor(s) at the level of pre-translation of the TGFbeta1 transcript and/or at the level of post-translation of the TGFbeta1 protein in the tumours. This process may be related to carcinogenesis and poses the question whether the suppression of the precursor TGFbeta1 is an early event, in vivo, in the human colorectal adenoma-carcinoma sequence.
Dimberg
J
J
Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping, Sweden. jan.dimberg@hhj.hj.se
Hugander
A
A
Sirsjo
A
A
D000236:Adenoma / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
D018076:DNA, Complementary; D011498:Protein Precursors; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1