MDR1 (multidrug resistance) gene expression in human primary liver cancer and cirrhosis

Chenivesse, Xavier; Franco, Dominique; Bréchot, Christian

doi:10.1016/s0168-8278(05)80243-0

Cited by 67 publications

(41 citation statements)

References 28 publications

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“…There have been several molecular targets associated with chemoresistance of hepatocellular carcinoma. Chemoresistance of hepatocellular carcinoma can be achieved by upregulation of the drug transporter family known as the adenosine triphosphate-binding cassette (ABC) transporters such as ABCB1, ABCC1, ABCC2, and ABCC3 (8)(9)(10)(11), leading to increment of drugs efflux system to remove drugs out of cells. High levels of MRP2, MRP3, MRP4, and MRP5 genes have been found in an acquired cisplatinresistant hepatocellular carcinoma cell line (12).…”

Section: Introductionmentioning

confidence: 99%

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Guo

et al. 2014

Molecular Cancer Therapeutics

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Chemoresistance is one of the major obstacles in systemic chemotherapy and targeted therapy for patients with advanced hepatocellular carcinoma. To identify novel chemoresistance-associated targets in hepatocellular carcinoma, chemoresistant hepatocellular carcinoma cell lines were established. By comparing the global gene expression profiles between chemoresistant and chemosensitive cell lines, eight novel chemoresistance-associated genes were identified to be significantly associated with the commonly augmented chemoresistance of hepatocellular carcinoma cells. One upregulated candidate named transmembrane protein 98 (TMEM98) was found to be overexpressed in 80 of 118 (67.80%) of patients with hepatocellular carcinoma. TMEM98 mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (P < 0.0001). Upregulation of TMEM98 was significantly correlated with advanced tumor stage (P ¼ 0.048), high incidence of early tumor recurrence (P ¼ 0.005), poor overall survival (P ¼ 0.029), and poor disease-free survival (P ¼ 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of TMEM98 mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (P ¼ 0.046). Moreover, patients with poor response to TACE treatment had higher degree of TMEM98 upregulation than the responsive patients. In vitro and in vivo studies showed that suppression of TMEM98 in chemoresistant hepatocellular carcinoma cells restored their chemosensitivity, while forced overexpression of TMEM98 enhanced their chemoresistance. The mechanism of TMEM98 in conferring chemoresistance of hepatocellular carcinoma might be possibly through activation of the AKT pathway and deactivation of p53. In conclusion, we identified a panel of novel common chemoresistance-associated genes and demonstrated that TMEM98 is a chemoresistanceconferring gene in hepatocellular carcinoma. Mol Cancer Ther; 13(5); 1285-97. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Guo

et al. 2014

Molecular Cancer Therapeutics

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“…The hallmark of the MDR phenotype in cancer cells is the overexpression of the energy-dependent efflux pump P-glycoprotein (P-gp; ref. 2), encoded by the MDR1 gene, which is commonly overexpressed in HCC (3,4). P-gp binds different amphipathic molecules, including chemotherapeutic agents that are exported out of the cell by ATP hydrolysis (5).…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte Growth Factor and Inducible Nitric Oxide Synthase Are Involved in Multidrug Resistance–Induced Angiogenesis in Hepatocellular Carcinoma Cell Lines

et al. 2006

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Based on literature, it is possible to hypothesize that multidrug resistance (MDR) and angiogenic phenotypes are linked to each other in human liver cancer cells. Our goal is to assess whether MDR cells trigger angiogenesis and to study the possible molecular mechanisms involved. Conditioned medium from parental drug-sensitive P5 cells (P5-CM) and MDR-positive P1(0.5) cells [P1(0.5)-CM] stimulated human umbilical vein endothelial cells (HUVEC) survival, proliferation, migration, and microtubular structure formation, but P1(0.5)-CM had a significantly greater effect than P5-CM. Cell implants were done in the rabbit avascular cornea to measure angiogenesis in vivo: P1(0.5) cells induced an important neovascular response in rabbit cornea after 1 week, whereas P5 cells had no effect. P1(0.5) and P5 cells produced vascular endothelial growth factor, but only P1(0.5) secreted hepatocyte growth factor (HGF) into the medium, and small interfering RNA specific for MDR1 clearly reduced HGF production in P1(0.5) cells. The transcription factor Ets-1 and the HGF receptor c-Met were up-regulated in P1(0.5) cells and in HUVEC cultured in P1(0.5)-CM. Inducible nitric oxide synthase (iNOS) seemed to play a major role in the proangiogenic effect of P1(0.5), and its inhibition by 1400W blunted the capacity of P1(0.5) cells to stimulate HUVEC proliferation, migration, and Ets-1 expression. In conclusion, these data show that development of MDR and angiogenic phenotypes are linked to each other in MDR cells. HGF production, Ets-1 and c-Met up-regulation, and iNOS expression can be part of the molecular mechanisms that enhance the angiogenic activity of the MDR-positive hepatocellular carcinoma cell line. (Cancer Res 2006; 66(5): 2673-82)

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“…Furthermore, the high expression of MDR results in the poor response of HCC to chemotherapy. 273 Thus it is a potential approach to treat HCC cells by composite delivery system co-loaded with siRNA for MDR genes and chemotherapeutic agent or multiple complementary chemotherapeutic agents to improve the prognosis of HCC. 274 …”

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confidence: 99%

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Li¹,

Zhang²,

Wang³

et al. 2016

IJN

117

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MDR1 (multidrug resistance) gene expression in human primary liver cancer and cirrhosis

Cited by 67 publications

References 28 publications

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Hepatocyte Growth Factor and Inducible Nitric Oxide Synthase Are Involved in Multidrug Resistance–Induced Angiogenesis in Hepatocellular Carcinoma Cell Lines

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

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