Hypoxia-inducible transcription factor (HIF)-1 alpha stabilization by actin-sequestering protein, thymosin beta-4 (TB4) in Hela cervical tumor cells.
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.
Oh
Jin-Mi
JM
Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
Ryoo
In-Ja
IJ
Yang
Young
Y
Kim
Hyun-Sun
HS
Yang
Kyu-Hwan
KH
Moon
Eun-Yi
EY
D000199:Actins / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013947:Thymosin / Q000378:metabolism / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000099201:Thymosin beta(4)
D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D048049:Extracellular Signal-Regulated MAP Kinases; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017239:Paclitaxel; D013947:Thymosin; D000099201:Thymosin beta(4)