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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한병리학회 Journal of Pathology and Translational Medicine Journal of Pathology and Translational Medicine 제45권 제3호
- 발행연도
- 2011.1
- 수록면
- 281 - 289 (9page)
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초록· 키워드
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Background: Multidrug resistance protein 1 (MDR1) encoded by ATP-binding cassette, sub-family B (Mdr/Tap), member 1 (ABCB1) mediates cross-resistance to antineoplastic drugs, and its expression is related to tumor aggressiveness. Methods: MDR1 expression was investigated in 100 hepatocellular carcinomas (HCCs) by immunohistochemical staining. The epigenetic mechanisms underlying ABCB1 transcriptional regulation were investigated in cell lines. Results: MDR1 was normally localized in the bile canalicular surface of the hepatocytes. Among 100 HCCs, 45 showed canalicular/luminal (CL) staining similar to the normal pattern, another 45 displayed membranous/cytoplasmic (MC) overexpression, and the remaining 10 revealed loss of expression. MC pattern or null staining of HCCs correlated with a higher histological grade and had a poorer prognosis than HCCs with a CL pattern (p<0.05). They also tended to have a poor prognosis by multivariate survival analysis. The ABCB1 promoter was hypomethylated regardless of MDR1 expression or ABCB1 mRNA levels in 10 HCC cell lines. Histone deacetylase inhibitor treatment induced ABCB1 upregulation in 4 cell lines with low or moderate ABCB1 levels. Conclusions: Our findings suggest that either an increase or a loss of MDR1 expression may contribute to the poor outcome of HCCs; histone deacetylation may be one of the epigenetic mechanisms directing the ABCB1 expression in HCCs.
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참고문헌 (25)
참고문헌 신청
Altekruse SF / 2009 / Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005 / J Clin Oncol 27 : 1485 ~ 1491
Baker EK / 2004 / MDR1, chemotherapy and chromatin remodeling / Cancer Biol Ther 3 : 819 ~ 824
Baker EK / 2005 / Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs / Oncogene 24 : 8061 ~ 8075
Befeler AS / 2002 / Hepatocellular carcinoma: diagnosis and treatment / Gastroenterology 122 : 1609 ~ 1619
Chen KG / 2005 / Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line / Cancer Res 65 : 9388 ~ 9397
Baker EK / 2004 / MDR1, chemotherapy and chromatin remodeling / Cancer Biol Ther 3 : 819 ~ 824
Baker EK / 2005 / Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs / Oncogene 24 : 8061 ~ 8075
Befeler AS / 2002 / Hepatocellular carcinoma: diagnosis and treatment / Gastroenterology 122 : 1609 ~ 1619
Chen KG / 2005 / Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line / Cancer Res 65 : 9388 ~ 9397
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