Decreased levels of precursor transforming growth factor beta(1) in human colorectal cancer

• Transforming growth factor (TGF) beta (1) is a growth factor with wide-ranging effects on proliferation, differentiation, immunosuppression, apoptosis and matrix remodelling. TGF beta (1) seems to have an antitumorigenic role in the gastrointestinal tract but may also be associated with the development of colorectal cancer. Initially, TGF beta (1) 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 TGF beta (1) protein expression (n=40) and TGF beta (1) 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 TGF beta (1) protein levels were generally lower in colorectal cancerous tissue compared to adjacent noncancerous tissue (P <0.001). Furthermore, with real-time PCR our results cannot reflect a statistically significant difference in TGF beta (1) gene expression between the tumour tissue and normal tissue. These finds indicate that it is likely that there are mechanisms which control precursor TGF beta (1) protein expression by factor(s) at the level of pre-translation of the TGF beta (1) transcript and/or at the level of post-translation of the TGF beta (1) protein in the tumours. This process may be related to carcinogenesis and poses the question whether the suppression of the precursor TGF beta (1) is an early event, in vivo, in the human colorectal adenoma-carcinoma sequence.

Nyckelord

TGF beta(1)

protein expression

colorectal cancer

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