4.7 Article

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

Journal

CANCER LETTERS
Volume 264, Issue 1, Pages 29-35

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.01.004

Keywords

thymosin beta-4; hela cell; hypoxia; HIF-1 alpha; ERK

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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)-1 alpha stabilization in cervical tumor cells, since TB4P reduced paclitaxel-induced cell death rate. TB4P increased HIF-1 alpha 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-1 alpha increased by TB4P. Paclitaxel-induced cell death was inhibited by hypoxia conditioning that increased HIF-1 alpha 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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