کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2115039 | 1084569 | 2008 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Hypoxia-inducible transcription factor (HIF)-1α stabilization by actin-sequestering protein, thymosin beta-4 (TB4) in Hela cervical tumor cells Hypoxia-inducible transcription factor (HIF)-1α stabilization by actin-sequestering protein, thymosin beta-4 (TB4) in Hela cervical tumor cells](/preview/png/2115039.png)
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.
Journal: Cancer Letters - Volume 264, Issue 1, 8 June 2008, Pages 29–35