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.
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.
Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer.
The availability of a weakly malignant model system in which TGF-alpha had demonstrable, but low level autocrine activity, permitted the investigation of the role of TGF-alpha in tumorigenesis by generating a stronger autocrine loop through the overexpression of the polypeptide.
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.
Low, mitogenic fluences of UVC (3.7-5.6 Jm-2) have previously been shown to cause increases of radioimmunoassayable transforming growth factor alpha (TGF alpha) in the medium and cells of cultures of melanocytes, melanoma lines, and HeLa cells (Ellem, K.A.O., Cullinan, M., Baumann, K.C., Dunstan, A.: Carcinogenesis 9:797-801, 1988).
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.
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.