Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells.
Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells.
复制标题
DOI：
10.1002/hep.25776
复制
发表时间：
2012-10
期刊：
影响因子：
13.5
通讯作者：
Bishop, J. Michael
中科院分区：
文献类型：
--
作者：
Chow, Edward Kai-Hua;Fan, Ling-ling;Chen, Xin;Bishop, J. Michael
At least some cancer stem cells (CSCs) display intrinsic drug resistance that may thwart eradication of a malignancy by chemotherapy. We have explored the genesis of such resistance by studying mouse models of liver cancer driven by either MYC or the combination of oncogenic forms of AKT and NRAS. A common manifestation of chemoresistance in CSCs is efflux of the DNA-binding dye Hoechst 33342. We found that only the MYC-driven tumors contained a subset of cells that efflux Hoechst 33342. This “side population” (SP) was enriched for CSCs when compared to non-SP tumor cells and exhibited markers of hepatic progenitor cells. The SP cells could differentiate into non-SP tumor cells, with coordinate loss of chemoresistance, progenitor markers and the enrichment for CSCs. In contrast, non-SP cells did not give rise to SP cells. Exclusion of Hoechst 33342 is mediated by ABC drug transporter proteins that also contribute to chemoresistance in cancer. We found that the MDR1 transporter was responsible for the efflux of Hoechst from SP cells in our MYC-driven model. Accordingly, SP cells and their tumor-initiating subset were more resistant than non-SP cells to chemotherapeutics that are effluxed by MDR1. The oncogenotype of a tumor can promote a specific mechanism of chemoresistance that can contribute to the survival of hepatic CSCs. Under circumstances that promote differentiation of CSCs into more mature tumor cells, the chemoresistance can be quickly lost. Elucidation of the mechanisms that govern chemoresistance in these mouse models may illuminate the genesis of chemoresistance in human liver cancer.
登录
查看更多内容
影响因子：
25.7
作者：
Kon, Junko;Ooe, Hidekazu;Mitaka, Toshihiro
通讯作者：
Mitaka, Toshihiro
DOI：
10.1073/pnas.1102454108
发表时间：
2011-05-10
影响因子：
11.1
作者：
Chaffer, Christine L.;Brueckmann, Ines;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
5.2
作者：
Ma, Stephanie;Chan, Kwok Wah;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan
影响因子：
45.3
作者：
Malogolowkin, Marcio H.;Katzenstein, Howard M.;Ortega, Jorge A.
通讯作者：
Ortega, Jorge A.
影响因子：
29.4
作者：
Chiba, Tetsuhiro;Zheng, Yun-Wen;Taniguchi, Hideki
通讯作者：
Taniguchi, Hideki