Therefore, in this study, patients with high TGF beta 1 protein levels in their primary site colorectal cancer were 18 times more likely to experience recurrence of their disease than were patients whose tumors exhibited low levels of TGF beta 1.
Frequent somatic mutations in a polyadenine (poly(A)) tract and two GT repeats within the coding region of the transforming growth factor beta (TGFbeta) receptor II (RII) gene were reported in colorectal cancers with MSI.
Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability.
Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI.
In summary, expression of the potential autocrine SCF/ c-kit axis is a tumor-associated phenomenon in colorectal cancer that can be suppressed by TGF-beta 1 in TGF-beta-responsive CRC cells.
The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis.
We assessed association of functional polymorphisms (-1082G/A; -592C/A) and TGF-beta1 (-509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case-control study of 62 patients and 124 matched controls.
Microsatellite unstable colorectal cancers (MSI-H CRCs) possess truncating mutations in the type II TGFbeta receptor (TGFbetaRII) gene that have been assumed to render these tumours insensitive to TGFbeta.
However, only limited information is available on genetic variation in the TGFB1 gene and its relationship to circulating levels and risk of colorectal cancer.
We have investigated if the presence of a common polymorphism in the TGFbeta receptor TGFBR1 might impact genomic instability in human colorectal cancer.
Our findings indicate that the distributions of polymorphisms in TGF-beta1 and its receptors genes vary greatly among different ethnic groups, and these polymorphisms might contribute to the colorectal cancer susceptibility.
These data suggest that the genetic polymorphism at -509 C/T but not at -800 G/A of the TGFB1 gene may play a role in susceptibility of Iranian subjects for colorectal carcinoma.
Transforming growth factor-beta1 (TGF-beta1) is overexpressed in a variety of malignant epithelial tumors and was suggested to be a marker of colorectal cancer.
As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.
We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N-terminal of the TGF-β1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function.