PMID- 18539158
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20131121
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 45
IP  - 4
DP  - 2008 Aug 15
TI  - Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in 
      tamoxifen-resistant breast cancer cells.
PG  - 537-46
LID - 10.1016/j.freeradbiomed.2008.05.011 [doi]
AB  - Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast 
      cancer patients. In this study, we found that the expressions of anti-oxidant 
      proteins (gamma-glutamylcysteine ligase heavy chain (gamma-GCL h), heme 
      oxygenase-1, thioredoxin and peroxiredoxin1) in TAM-resistant MCF-7 (TAMR-MCF-7) 
      cells were higher than control MCF-7 cells. Molecular analyses using antioxidant 
      response element (ARE)-containing reporters and gel-shift supported the critical 
      role of NF-E2-related factor2 (Nrf2)/ARE in the overexpression of antioxidant 
      proteins in TAMR-MCF-7 cells. Intracellular peroxide production was significantly 
      decreased in TAMR-MCF-7 cells and TAM resistance was partially reversed by Nrf2 
      siRNA. The basal phosphorylation of extracellular signal-regulated kinase (ERK) 
      and p38 kinase were increased in the TAMR-MCF-7 cells and the inhibition of ERK 
      significantly decreased the activity of minimal ARE reporter and gamma-GCL h 
      protein expression in TAMR-MCF-7 cells. However, exposure of TAMR-MCF-7 cells to 
      17-beta-estradiol or ICI-182,780 did not significantly change gamma-GCL h 
      expression. These results suggest that the persistent activation of Nrf2/ARE is 
      critical for the enhanced expression of anti-oxidant proteins in TAM-resistant 
      breast cancer cells and the pathway of ERK, but not of estrogen receptor 
      signaling are involved in the up-regulation of Nrf2/ARE.
FAU - Kim, Sang Kyum
AU  - Kim SK
AD  - College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam 
      National University, Daejeon, South Korea.
FAU - Yang, Jin Won
AU  - Yang JW
FAU - Kim, Mi Ra
AU  - Kim MR
FAU - Roh, Sang Hee
AU  - Roh SH
FAU - Kim, Hyung Gyun
AU  - Kim HG
FAU - Lee, Kwang Youl
AU  - Lee KY
FAU - Jeong, Hye Gwang
AU  - Jeong HG
FAU - Kang, Keon Wook
AU  - Kang KW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080524
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Estrogen)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
SB  - IM
MH  - Antineoplastic Agents, Hormonal/*pharmacology
MH  - Antioxidants/*metabolism
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - *Drug Resistance, Neoplasm
MH  - Glutamate-Cysteine Ligase/metabolism
MH  - Humans
MH  - NF-E2-Related Factor 2/*metabolism
MH  - NF-kappa B/metabolism
MH  - RNA, Small Interfering
MH  - Receptors, Estrogen/metabolism
MH  - Signal Transduction
MH  - Tamoxifen/*pharmacology
EDAT- 2008/06/10 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/06/10 09:00
PHST- 2007/10/15 00:00 [received]
PHST- 2008/05/08 00:00 [revised]
PHST- 2008/05/15 00:00 [accepted]
PHST- 2008/06/10 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/06/10 09:00 [entrez]
AID - S0891-5849(08)00302-X [pii]
AID - 10.1016/j.freeradbiomed.2008.05.011 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2008 Aug 15;45(4):537-46. doi: 
      10.1016/j.freeradbiomed.2008.05.011. Epub 2008 May 24.