Document Detail


ERK activation by thymosin-beta-4 (TB4) overexpression induces paclitaxel-resistance.
MedLine Citation:
PMID:  16515784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of paclitaxel-resistance in tumors is one of the most significant obstacles to successful therapy. Thymosin-beta-4 (TB4) has been known as actin-sequestering protein and functions in tumor metastasis. Here, we overexpressed TB4 in HeLa cells (TB4-HeLa) and examined the effect of TB4 in paclitaxel-induced cell death. TB4-HeLa cells showed a higher growth rate and a lower percentage of basal apoptosis than HeLa cells. TB4-HeLa cells were more resistant to paclitaxel-induced cell death than HeLa cells. TB4 transcript expression with paclitaxel treatment was dose-dependently increased in HeLa cells but that was not in TB4-HeLa cells. Small interfering RNA (siRNA) of TB4 inhibited HeLa cell growth and enhanced paclitaxel-induced cell death. Basal ERK phosphorylation was elevated and basal p38 kinase phosphorylation was reduced in paclitaxel non-treated TB4-HeLa cells. When treated with paclitaxel, cell death and resistance-induction were independent of ERK and p38 kinase activation. Paclitaxel-resistance of TB4-HeLa cells was overcome by the inhibition of basal ERK activity with PD98059 pre-treatment. The inhibition of basal p38 kinase activity with SB203580 pre-treatment attenuated the paclitaxel-induced HeLa cell death. In conclusion, TB4 induced paclitaxel-resistance through the elevation of basal level of ERK phosphorylation. Therefore, TB4 could be a novel target to regulate paclitaxel-resistance.
Authors:
Su-Young Oh; Ji-Hee Song; Jung-Eun Gil; Jeong-Hee Kim; Young-Il Yeom; Eun-Yi Moon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-03
Journal Detail:
Title:  Experimental cell research     Volume:  312     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-02     Completed Date:  2006-07-21     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1651-7     Citation Subset:  IM    
Affiliation:
Department of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Taejeon 305-806, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects,  genetics
Cell Proliferation
Cell Survival / drug effects,  genetics
Drug Resistance, Neoplasm / genetics*
Enzyme Activation
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flavonoids / pharmacology
Gene Expression Regulation, Neoplastic
HeLa Cells
Humans
Imidazoles / pharmacology
Mice
NIH 3T3 Cells
Paclitaxel / pharmacology*
Phosphorylation / drug effects
Pyridines / pharmacology
RNA, Small Interfering / genetics
Thymosin / genetics*,  metabolism
Transfection
p38 Mitogen-Activated Protein Kinases / metabolism
ras Proteins / genetics
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Antineoplastic Agents, Phytogenic; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Pyridines; 0/RNA, Small Interfering; 0/SB 203580; 33069-62-4/Paclitaxel; 61512-21-8/Thymosin; 77591-33-4/thymosin beta(4); EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.6.5.2/ras Proteins

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


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