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

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

doi:10.1016/j.febslet.2008.06.036

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

Hyun Bark
, Hai Dong Xu
, Sang Hyun Kim
, Jisoo Yun
, Cheol Hee Choi

Department of Medicine

Chosun University

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2595-2600
Number of pages	6
Journal	FEBS Letters
Volume	582
Issue number	17
DOIs	https://doi.org/10.1016/j.febslet.2008.06.036
State	Published - 23 Jul 2008

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Breast cancer resistance protein
c-Jun
c-Jun NH2-terminal kinase
P-glycoprotein
PSC833
Verapamil

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10.1016/j.febslet.2008.06.036

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title = "P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state",

abstract = "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.",

keywords = "Breast cancer resistance protein, c-Jun, c-Jun NH2-terminal kinase, P-glycoprotein, PSC833, Verapamil",

author = "Hyun Bark and Xu, \{Hai Dong\} and Kim, \{Sang Hyun\} and Jisoo Yun and Choi, \{Cheol Hee\}",

year = "2008",

month = jul,

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doi = "10.1016/j.febslet.2008.06.036",

language = "English",

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T1 - P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state

AU - Bark, Hyun

AU - Xu, Hai Dong

AU - Kim, Sang Hyun

AU - Yun, Jisoo

AU - Choi, Cheol Hee

PY - 2008/7/23

Y1 - 2008/7/23

N2 - 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.

AB - 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.

KW - Breast cancer resistance protein

KW - c-Jun

KW - c-Jun NH2-terminal kinase

KW - P-glycoprotein

KW - PSC833

KW - Verapamil

UR - https://www.scopus.com/pages/publications/46749098226

U2 - 10.1016/j.febslet.2008.06.036

DO - 10.1016/j.febslet.2008.06.036

M3 - Article

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AN - SCOPUS:46749098226

SN - 0014-5793

VL - 582

SP - 2595

EP - 2600

JO - FEBS Letters

JF - FEBS Letters

IS - 17

ER -

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

Abstract

UN SDGs

Keywords

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