Document Detail


Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells.
MedLine Citation:
PMID:  22427054     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells.
Authors:
Zhihua Li; Na Wang; Jieyu Fang; Jintao Huang; Fen Tian; Chaohong Li; Fukang Xie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-15
Journal Detail:
Title:  Oncology reports     Volume:  27     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-04-09     Completed Date:  2012-08-27     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1879-86     Citation Subset:  IM    
Affiliation:
Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Antineoplastic Agents, Hormonal / pharmacology
Apoptosis / drug effects*
Benzopyrans / pharmacology
Breast Neoplasms / drug therapy*,  genetics,  metabolism*,  pathology
Carbazoles
Cell Line, Tumor
Cell Proliferation
Cell Survival / drug effects
Drug Resistance, Neoplasm*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Flavonoids / pharmacology
Humans
Protein Kinase C-alpha / metabolism
Protein Kinase C-delta / metabolism
Receptors, Estrogen / biosynthesis
Signal Transduction / drug effects
Tamoxifen / pharmacology*
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Acetophenones; 0/Antineoplastic Agents, Hormonal; 0/Benzopyrans; 0/Carbazoles; 0/Flavonoids; 0/Receptors, Estrogen; 10540-29-1/Tamoxifen; 136194-77-9/Go 6976; E29LP3ZMUH/rottlerin; EC 2.7.11.13/Protein Kinase C-alpha; EC 2.7.11.13/Protein Kinase C-delta; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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