Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma

BMC Gastroenterology

Research Article

Devis Pascut¹  Natalia Rosso¹  Caecilia HC Sukowati¹  Beatrice Anfuso¹  Claudio Tiribelli²  Lory S Crocè²  Giuliano Torre³  Paola Francalanci³ 

[1] Centro Studi Fegato, Fondazione Italiana Fegato, Bld Q AREA Science Park Basovizza, Trieste, Italy;Centro Studi Fegato, Fondazione Italiana Fegato, Bld Q AREA Science Park Basovizza, Trieste, Italy;Department of Medicine, University of Trieste, 34100, Trieste, Italy;Ospedale Pediatrico Bambino Gesù, 00100, Rome, Italy;

关键词: Liver cancer;    Drug resistance;    Gene expression;    Doxorubicin;   

DOI  :  10.1186/1471-230X-12-160

 received in 2012-07-23, accepted in 2012-11-01,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy.MethodsIn cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot.ResultsABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC.ConclusionsOur results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.

【 授权许可】

CC BY   
© Sukowati et al.; licensee BioMed Central Ltd. 2012