Vol 9: PTEN Regulates BCRP-ABCG2 and the Side Population through the PI3K-Akt Pathway in Chronic Myeloid Leukemia.Report as inadecuate



 Vol 9: PTEN Regulates BCRP-ABCG2 and the Side Population through the PI3K-Akt Pathway in Chronic Myeloid Leukemia.


Vol 9: PTEN Regulates BCRP-ABCG2 and the Side Population through the PI3K-Akt Pathway in Chronic Myeloid Leukemia. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 9: PTEN Regulates BCRP-ABCG2 and the Side Population through the PI3K-Akt Pathway in Chronic Myeloid Leukemia.
This article is from PLoS ONE, volume 9.AbstractA small population of cancer stem cells named the -side population- SP has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors TKIs, results in therapeutic failure or refractory-relapsed disease in chronic myeloid leukemia CML. The drug pump, ATP-binding cassette sub-family G member 2 ABCG2, is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K-Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562-ABCG2 ABCG2 overexpressing and K562-IMR resistance to imatinib cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 PTEN and activated phosphorylated-Akt p-Akt. PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase-blastic phase AP-BP, increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K-Akt pathway, which would be a potentially effective strategy for targeting CML stem cells.



Author: Huang, Fang-Fang; Zhang, Li; Wu, Deng-Shu; Yuan, Xiao-Yu; Chen, Fang-Ping; Zeng, Hui; Yu, Yan-Hui; Zhao, Xie-Lan

Source: https://archive.org/







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