BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by multicause, obvious multistage and multifocal processes of tumor progression. The development of HCC is related intimately to overexpression and signal transduction of many cellular factors. This study was undertaken to investigate the dynamic expression and alteration of heat shock protein (HSP) gp96 along with its gene during HCC development.
METHODS: A rat model of hepatoma induced with 2-fluorenylacetamide (2-FAA, 0.05%) was established in male Sprague-Dawley rats. Total RNA and pathological changes were observed during hepatocarcinogenesis. Total RNAs were transcribed into cDNA by reverse transcription and the gene fragment of gp96 was amplified by nested RT-PCR. The gp96 expression in rat liver tissues was semi-quantitatively analyzed by immunohistochemistry.
RESULTS: Histological examination suggested  that  hepatocytes in rats fed with 2-FAA showed vacuole-like denaturation at the early stages, then dysplastic nodules appeared at the middle stage, and finally progressed to tubercles of cancerous nests. A tendency of increasing liver gp96 protein level was found from normal liver to precancerous to cancerous tissues during hepatoma development (P<0.01), and was in accordance with the changes in gp96 mRNA (P<0.05).
CONCLUSION: HSP gp96 is involved in HCC development and its overexpression may be a useful marker for early diagnosis.