Investigation of the role of activated Kras in hepatic transdifferentiation of pancreas

• Main Authors: Chi-Che Hsieh, 謝綺哲
• Other Authors: Chia-Ning Shen
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/04948184186555198766

碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 95 === ABSTRACT Pancreas cancer is the tenth leading cause of death in Taiwan. Because of lacking a sensitive method to diagnose pancreatic cancer patients at early phase, most pancreatic cancer was metastasized at the time of diagnosis. Therefore, the overall five years survival rate of pancreatic cancer patients was only 4% suggesting further studies on molecular basis is needed for developing a new method in detection of early pancreatic carcinogenesis. Appearance of intraepithelial neoplasia are well-documented in cases of pancreatic cancer, which were possibly resulted from abonormal activation of EGF/TGFalpha and Ras signaling pathway. In fact, clinical reports indicate that activated Kras mutations were detected in nearly 100% of pancreatic adenocarcinoma. Furthermore, recent findings also indicate hepatic metaplsia (or transdifferentiation), which was possibly regulated by C/EBPbeta□and glucocorticoids/Oncostain M, was sometimes obtained in pancreatic cancer patients. In current study, we demonstrated that activation of Ras signaling was obtained in hepatic transdifferentiation. In contrast, inhibition of Ras activation with farnesylthiosalicylic acid (FTS) was sufficient to downregulate hepatic transdifferentiation. Moreover, activated of Ras signaling by GTPgammaS treatment or by overexpresion of activated Kras mutant (KrasG12D) would enhanced hepatic transdifferentiation. Taken together, our current findings possibly provide a molecular cue to explain the possibility of observation of hepatic metaplsia in pancreatic cancer patients.