Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the can...Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the "cancer stem cell hypothesis", which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells(liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future.展开更多
Background Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase （MEK） 1 and 2 in the regulation of human insulin...Background Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase （MEK） 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells. Methods In the absence or presence of a selective inhibitor for MEK1 （PD98059） or a specific siRNA for MEK2 （siMEK2）, with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit （CCK）-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting. Results T24 cell proliferation was promoted by PD98059 at 5-20 IJmol/L, inhibited by siMEK2 at 25-100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERKI/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERKI/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected. Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.展开更多
基金Supported by The Special Research Foundation of the National Natural Science Foundation of China,No.81172068
文摘Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the "cancer stem cell hypothesis", which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells(liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81070598）.
文摘Background Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase （MEK） 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells. Methods In the absence or presence of a selective inhibitor for MEK1 （PD98059） or a specific siRNA for MEK2 （siMEK2）, with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit （CCK）-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting. Results T24 cell proliferation was promoted by PD98059 at 5-20 IJmol/L, inhibited by siMEK2 at 25-100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERKI/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERKI/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected. Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.
