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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 109 - 117 (9page)
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The mutation and reduction of mitochondrial DNA (mtDNA) have been suggested as factors in the car-cinogenesis. However, whether the depletion of mtDNA induces multidrug resistance in cancer cells has not been fuly investigated. To elucidate the asso-ciation of cellular mtDNA content and drug resistance, a marked decrease in cellular mtDNA and ATP content, concomitant with a lack of mRNAs encoded by mtDNA. The mtDNA-depleted cels showed a decreased sensi-tivity and accumulation of anti-cancer drugs, sugest-ing that mtDNA depletion could develop multidrug re-sistance (MDR) phenotype in HCT-8 cells. We found that the expression level of MDR1 mRNA and its trans-lated product P-glycoprotein was increased in the sensitivity and accumulation of anti-cancer drug in the mtDNA-depleted cells might be due to a substantial in-crease in the expression of P-glycoprotein. Further-more, increased expression of MDR1 mRNA and P-gly-coprotein was due to an increase of mRNA stability rather than transcriptional activation. Taken together, these results indicate that mtDNA depletion can induce an increased P-glycoprotein expression via an in-crease of mRNA stability and suggest that the mtDNA depletion in cancer cells plays an important role in the induction of MDR phenotype.
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참고문헌 (24)
참고문헌 신청
Amuthan G / 2001 / Vijayasarathy C, Avadhani NG. Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion / Embo J 20 : 1910 ~
Amuthan G / 2002 / Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells / Oncogene 21 : 7839 ~ 49
Bentires-Alj M / 2003 / NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells / Oncogene 22 : 90 ~ 7
Biswas G / 1999 / Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk /
Biswas G / 2005 / Anandatheerthavarada HK, Avadhani NG. Mechanism of mitochondrial stress-induced resistance to apoptosis in mitochondrial DNA-depleted C2C12 myocytes / Cell
Amuthan G / 2002 / Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells / Oncogene 21 : 7839 ~ 49
Bentires-Alj M / 2003 / NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells / Oncogene 22 : 90 ~ 7
Biswas G / 1999 / Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk /
Biswas G / 2005 / Anandatheerthavarada HK, Avadhani NG. Mechanism of mitochondrial stress-induced resistance to apoptosis in mitochondrial DNA-depleted C2C12 myocytes / Cell
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