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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 174 - 180 (7page)
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Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance to paclitaxel in v-H-ras transformed NIH 3T3 fibroblasts (Ras-NIH 3T3). We established a multidrug-resistant cell line (Ras-NIH 3T3/Mdr) from Ras-NIH 3T3 cells by stepwise increases in paclitaxel. Drug sensitivity assays indicated that the $IC_{50}$ value for drug-resistant Ras-NIH 3T3/Mdr cells was more than 1 ${\mu}M$ paclitaxel, 10- or more-fold higher than for the parental Ras-NIH 3T3 cells. Western blot and RT-PCR analysis showed that the drug efflux pump a P-glycoprotein were highly expressed in Ras-NIH 3T3/Mdr cells, while not being detectable in Ras-NIH 3T3 cells. Additionally, verapamil, which appears to inhibit drug efflux by acting as a substrate for P-glycoprotein, completely reversed resistance to paclitaxel in Ras-NIH 3T3/Mdr cell line, indicating that resistance to paclitaxel is associated with overexpression of the multidrug resistance gene. Interestingly, Ras-NIH 3T3/Mdr cells have higher basal Raf-1 activity compared to Ras-NIH 3T3 cells. Unexpectedly, however, the colocalization of Raf-1 and its negative regulator Spry2 was less observed in cytoplasm of Ras-NIH 3T3/Mdr cells due to translocation of Spry2 around the nucleus in the perinuclear zone, implying that Raf-1 may be released from negative feedback inhibition by interacting with Spry2. We also showed that shRNA-mediated knockdown of Raf-1 caused a moderate increase in cell susceptibility to paclitaxel. Thus, the results presented here suggest that a Raf-1-dependent pathway plays an important role in the development of acquired drug-resistance.
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참고문헌 (31)
참고문헌 신청
Abrams, S. L / 2010 / The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy / Cell Cycle 9:1781~1791
Ahn, J. H. / 2009 / The enhancement of Raf-1 kinase activity by knockdown of Spry2 is associated with high sensitivity to paclitaxel in v-Ha-ras-transformed NIH 3T3 fibroblasts / MOLECULAR AND CELLULAR BIOCHEMISTRY 332:189~197
Jun-Ho Ahn / 2010 / Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts / BMB reports 43(3):205~211
Blobe, G. C / 1993 / Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional signifi cance of enhanced expression of PKC alpha / J. Biol. Chem 268:658~664
Callaghan, R / 1995 / Interaction of tamoxifen with the multidrug resistance P-glycoprotein / Br. J. Cancer 71:294~299
Ahn, J. H. / 2009 / The enhancement of Raf-1 kinase activity by knockdown of Spry2 is associated with high sensitivity to paclitaxel in v-Ha-ras-transformed NIH 3T3 fibroblasts / MOLECULAR AND CELLULAR BIOCHEMISTRY 332:189~197
Jun-Ho Ahn / 2010 / Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts / BMB reports 43(3):205~211
Blobe, G. C / 1993 / Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional signifi cance of enhanced expression of PKC alpha / J. Biol. Chem 268:658~664
Callaghan, R / 1995 / Interaction of tamoxifen with the multidrug resistance P-glycoprotein / Br. J. Cancer 71:294~299
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