ERK activation by Thymosin-beta-4 (TB4) overexpression induces paclitaxel-resistance

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ERK activation by Thymosin-beta-4 (TB4) overexpression induces paclitaxel-resistance
Su-Young Oh; Jun Hee Lee; Jung-Eun Gil; J H Kim; Young Il Yeom; Eun Yi Moon
Bibliographic Citation
Experimental Cell Research, vol. 312, no. 9, pp. 1651-1657
Publication Year
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.
ERKHeLa cellPaclitaxelResistanceThymosin-beta-4
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Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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