EXPRESSION OF TGF-alpha AND TGF-beta

ABSTRACT

epigenetic alterations have been identified in hamster and carcinogenesis model, there is no information about the possible role of transforming growth factor related with oral cancer. The purpose of this paper was to find the expression patterns of transforming growth factor alpha and beta during the stages of complete oral carcinogenesis model in hamster. 0.5% 9, 10-dimethyl-1, 2-benzanthracene(DMBA) in mineral oil was topically applied to the buccal pouch of 75 hamster three times a week during the experimental periods. The experimental animals were subdivided into two groups of control and experiment. Only the mineral oil was applied to the control group. 0.5% DMBA in mineral oil was applied to the experimental groups of 6, 8, 10, 12, 14, 16, 18 and 20 weeks. The expression of the TGF-alpha and TGF-beta protein were evaluated by the distribution and intensity of positive cells during the carcinogenesis using the immunohistochemical study. The following results were obtained ; 1. The buccal pouch epithelium of hamster was histologically changed to the dysplasia at 6, 8, 10 weeks, carcinoma in situ at 12 weeks, and squamous cell carcinoma at 14 weeks. 2. The expression of the TGF-alpha was restricted to the parabasal and basal layers of the normal and dysplastic mucosa, but those positive cells were extended to the spinous layers of the epithelium in the carcinoma. 3. The degree of TGF-alpha expression was markedly decreased in the carcinoma at 16, 18, 20. The strong positive staining in the center of cancer islands and weak positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. 4. The positive index of the TGF-alpha had a tendency to increase with DMBA- applied time. There was a statistically significant difference between 12, 18, 20 experimental group and control group(p<0.05). 5. The expression of TGF-beta was shown at the cytoplasm of all control and experimental groups, and the parabasal and basal layers of the normal and dyslastic mucosa, but it was shown at the basal layers of the epithelium in the carcinoma. 6. TGF-beta was expressed diffusely at 16, 18, 20 experimental gruop. The strong positive staining in the center of cancer islands and positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. Form the above finding, the expression of TGF-alpha and TGF-beta in oral carcinogenesis model seems to have two formal stages, the first being an overexpression step as reaction to uncontrolled growth and the second being one in which exteral protein accumulate in the surrounding stroma and intracytoplasm. Overexpression of TGF-alpha and TGF-beta may have important cooperative roles for the promotion of cancer and factor of prognosis.