P‐glycoprotein down‐regulates expression of breast cancer resistance protein in a drug‐free state | Zendy

Bark Hyun | Zendy; Xu Hai-Dong | Zendy; Kim Sang-Hyun | Zendy; Yun Jisoo | Zendy; Choi Cheol-Hee | Zendy

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P‐glycoprotein down‐regulates expression of breast cancer resistance protein in a drug‐free state

Author(s) -

Bark Hyun,

Xu Hai-Dong,

Kim Sang-Hyun,

Yun Jisoo,

Choi Cheol-Hee

Publication year - 2008

Publication title -

febs letters

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.593

H-Index - 257

eISSN - 1873-3468

pISSN - 0014-5793

DOI - 10.1016/j.febslet.2008.06.036

Subject(s) - abcg2 , p glycoprotein , western blot , c jun , kinase , verapamil , cell culture , multiple drug resistance , chemistry , microbiology and biotechnology , atp binding cassette transporter , cancer research , drug resistance , pharmacology , biology , biochemistry , transporter , transcription factor , gene , genetics , organic chemistry , calcium

This study investigated whether P‐glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are linked in terms of expression. RT‐PCR and Western blot analyses showed that the lung cancer cell line SK‐MES‐1/WT expressed BCRP. In a drug‐free state, BCRP expression was significantly down‐regulated in doxorubicin‐resistant SK‐MES‐1/DX1000 cells overexpressing Pgp. Pharmacological inhibitors (PSC833 or verapamil) or siRNA for Pgp inhibited the down‐regulation of BCRP, which was confirmed by confocal microscopy. PSC833 induced the phosphorylation of c‐Jun NH2‐terminal kinase (JNK) and c‐Jun, while the JNK inhibitor SP600125 inhibited this effect. Dominant negative c‐Jun decreased the expression of BCRP, but increased that of Pgp. These results indicate that Pgp down‐regulates BCRP expression in a drug‐free state in which JNK/c‐Jun is involved.

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