| Summary: | 碩士 === 國立成功大學 === 生物化學研究所 === 93 === Endoplasmic reticulum(ER) is the first compartment of secretory pathway to modify and fold the proteins. When misfolded or unfolded proteins accumulate in the ER, cells activate a self-protective mechanism, termed the ER stress response. Hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic liver diseases. In HBV-associated hepatocarcinoma, the large HBsAg with deletions in pre-S1 or pre-S2 region have been detected. These pre-S mutant HBsAg accumulate in endoplasmic reticulum (ER), resulting in ER stress. Specifically, expressoion of pre-S2�� is associated with potential carcinogenesis. Since c-jun is essential important for hepatocyte development. We wish investigate whether there is a linkage between HBV pre-S mutant, ER stress, and c-jun. Tunicamycin and brefeldin A, two ER stress inducers, increase the expression of c-Jun in ML-1 cells. Expression of pre-S mutant HBsAg also enhance the expression of c-Jun in ML-1 cells. Furthermore, one of the c-Jun regulated gene, MMP-9, was increased under ER stress. MMP-9 is known to play a key role in cancer invasion and metastasis by degradating the extracellular matrix (ECM) and basement membrane barriers. Since AP-1 acts on the promoter of MMP-9 gene, we further demonstrate that enhanced binding of c-Jun on the promoter of MMP-9 under ER stress. ML-1 cells expressing wild type or mutant HBV surface protein is associated with the expression of c-Jun and MMP-9. In addition, higher migration ability was observed in ML-1 cells expressed pre-S2 mutant compared with that of wild type pre-S.
|
|---|
