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Title 

Hypoxia-inducible transcription factor (HIF)-1α stabilization by actin-sequestering protein, thymosin beta-4 (TB4) in Hela cervical tumor cells

Authors 

J M OhIn Ja RyooY YangH S KimK H YangE Y Moon

Publisher 

Elsevier

Issue Date 

2008

Citation 

Cancer Letters, vol. 264, no. 1, pp. 29-35

Keywords 

ERKhela cellHIF-1αhypoxiathymosin beta-4hypoxia inducible factor 1alphamitogen activated protein kinasemitogen activated protein kinase inhibitorthymosin beta4cell hypoxia

Abstract 

Thymosin beta-4 (TB4) is an actin-sequestering protein to control cytoskeletal reorganization. Here, we investigated whether TB4 proteins (TB4P) affect tumor microenvironment by measuring hypoxia-inducible transcription factor (HIF)-1α stabilization in cervical tumor cells, since TB4P reduced paclitaxel-induced cell death rate. TB4P increased HIF-1α stabilization and transactivation, which is measured by the increase of hypoxia response element (HRE)-luciferase activity and target gene, vascular endothelial growth factor (VEGF) transcription. TB4P also elevated ERK phosphorylation. PD98059, ERK inhibitor reduced HIF-1α increased by TB4P. Paclitaxel-induced cell death was inhibited by hypoxia conditioning that increased HIF-1α stabilization and ERK phosphorylation. PD98059 reversed paclitaxel-induced cell death which was attenuated by hypoxia. Collectively, TB4P could lead tumor cell microenvironment to hypoxia condition, which might be resulted in antitumor drug-resistance induction. It suggests that soluble TB4P could be a novel target to control tumor cell death by regulating tumor cell microenvironment.

ISSN 

0304-3835

Link 

http://dx.doi.org/10.1016/j.canlet.2008.01.004

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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