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 tr...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.展开更多
Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo ...Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.展开更多
基金The study was supported by grants-in-aid from the Key Project of Medical Science of Jiangsu Province, China (RC2003100)the Science and Technology Project for Social Development of Nantong, China (No. S40034).
文摘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.
基金This project was supported by the National Natural Sciences Foundation of China (No. 30171089).
文摘Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.
