These results suggest that in endocrine tissues, TGF-alpha is unlikely to prove useful as a tumor marker but that the growth factor may play a role in both normal physiology and tumorigenesis.
TGF-alpha/EGFR autocrine signaling appears to play an important role in squamous cell carcinoma of the head and neck (SCCHN) and upregulation of TGF-alpha and EGFR is an early event in SCCHN carcinogenesis.
Although the frequent detection of both TGFalpha protein and its mRNA, as well as of EGF/TGFalpha receptor within tumors of all type and grades, suggests that TGFalpha serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain.
EGFR is over-expressed in up to 90-100% of head-and-neck squamous cell carcinomas (HNSCC), and increased expression of EGFR and its ligand Transforming Growth Factor-alpha (TGF-alpha) is not limited to malignant cells, but also detected in histologically normal mucosa of HNSCC patients, supporting the hypothesis of field carcinogenesis.
TGF-alpha and EGFR protein expression is increased early in head and neck squamous cell carcinogenesis and can be quantitated by computerized image analysis of immunohistochemical staining.
Consequently, tumor cells lacking pVHL overproduce the products of HIF target genes such as vascular endothelial growth factor and transforming growth factor alpha. pVHL has been implicated in a variety of processes that are central to carcinogenesis including cell-cycle control, differentiation, extracellular matrix formation and turnover, and angiogenesis.
Increasing the level of TGF-alpha production by the NRK-49F cells in this way was sufficient to promote agar growth of the cells in the presence of TGF-beta but insufficient to promote tumorigenesis.
Our results are consistent with an autocrine role for TGF-alpha and EGF-R in oesophageal carcinogenesis and support the possibility that c-myc overexpression may be required for the in vivo tumourigenicity of cells that produce high levels of TGF-alpha and the EGF-R.
Transforming growth factor-alpha (TGF-alpha) contributes to the progression of mammary carcinogenesis in part through synergistic augmentation of estradiol (E2) action.
Role of transforming growth factor-alpha in von Hippel--Lindau (VHL)(-/-) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis.
Since EGF is known to induce proliferation and dedifferentiation of normal thyroid cells in culture, TGF-alpha and its receptor may play an important role in thyroid carcinogenesis.
We believe that the PB-dependent modification of tumorigenesis in the livers of c-myc/TGF-alpha mice was predominantly a result of the ability of this drug to block cell death during the early stages of tumor development.
In this study, we investigated the ability of prolactin to modulate carcinogenesis when co-expressed with the potent oncogene transforming growth factor alpha (TGFalpha) in bitransgenic mice.