TRANSFORMING GROWTH FACTOR-α EXPRESSION IS ALTERED DURING EXPERIMENTAL HEPATOCARCINOGENESIS

✍ Scribed by BURR, ANDREW W.; TOOLE, KIERAN; MATHEW, JOSEPH; HINES, JULIE E.; CHAPMAN, CLAIRE; BURT, ALASTAIR D.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 948 KB
• Volume: 179
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(199607)179:3<276::aid-path573>3.0.co;2-u

✦ Synopsis

In order to characterize the role of transforming growth factor-a (TGFa) during hepatocarcinogenesis, liver tissue was examined at 10, 16, and 19 weeks following initial 10-week diethylnitrosamine (50 mg Idrinking water) exposure in female Wistar rats. Liver tissue protein extracts were electrophoresed and transferred to nitrocellulose filters. Levels of tissue-derived TGFa and epidermal growth factor receptor (EGFr) were assessed using an anti-TGFa monoclonal antibody (Ab-1) and an anti-EGFr polyclonal antibody (AB-4), coupled with scanning densitometric quantification. Immunolocalization of TGFa was performed in Bouin's-fixed, paraffin-embedded liver tissue sections. The distribution and intensity of TGFa immunoreactivity varied according to the degree of dysplasia, severely dysplastic cells being strongly immunoreactive. At week 10, mild hepatocyte dysplasia and perivenular inflammation were evident, together with a corresponding increase in perivenular TGFa immunoreactivity. By week 16, foci of moderate to severe dysplasia were observed; at this stage, there was a decrease in perivenular immunoreactivity but a further increase in overall liver tissue TGFa levels. Some 'altered foci' and dysplastic nodules showed intense immunoreactivity for TGFa. At these time points, immunodetectable liver EGFr was found to decrease significantly in comparison with normal control tissue. TGFa immunoreactivity was observed in fully developed carcinomas at week 19, although some tumours were negative by immunohistochemistry. The up-regulation of immunodetectable TGFa and the concomitant down-regulation of EGFr demonstrated positive (P<O*Ol) and negative (P<O.OOl) correlations, respectively, with hepatocyte proliferation indices. These findings suggest that the TGFalEGFr ligand receptor system may be important during tumour promotion and in the stimulation of continued proliferation in hepatocellular carcinomas.