| Literature DB >> 22988121 |
Xin Ma1, Yanfei Cai, Dongxu He, Chang Zou, Peng Zhang, Chun Yin Lo, Zhenyu Xu, Franky L Chan, Shan Yu, Yun Chen, Ruiyu Zhu, Jianyong Lei, Jian Jin, Xiaoqiang Yao.
Abstract
An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca(2+)-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.Entities:
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Year: 2012 PMID： 22988121 PMCID： PMC3479621 DOI： 10.1073/pnas.1202989109
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205