Back to Search
Start Over
The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3β in hepatocellular carcinoma
- Source :
-
Journal of Hepatology . Feb2004, Vol. 40 Issue 2, p212. 7p. - Publication Year :
- 2004
-
Abstract
- Background/Aims: The organic anion transporting polypeptides (OATPs) mediate the uptake of numerous amphipathic compounds into hepatocytes. Our aim was to study the expression and regulation of OATP8 (OATP1B3, SLC21A8/SLCO1B3) and OATP-C (OATP1B1, SLC21A6/SLCO1B1) in hepatocellular carcinomas (HCC).Methods: RNA and protein levels in 13 paired HCC and adjacent non-tumor liver samples were quantified by real-time polymerase chain reaction or Western blot, respectively. The OATP8 and OATP-C gene promoters were characterized by luciferase reporter assays and electrophoretic mobility shift assays (EMSA).Results: The expression of OATP8 was decreased in 60% of HCC compared to surrounding non-tumor liver tissue, on both the mRNA and protein levels. Expression of the liver-enriched transcription factor hepatocyte nuclear factor 3β (HNF3β) was increased in 70% of HCC and correlated inversely with OATP8 mRNA (r=−0.75, P<0.05) and protein. In contrast to OATP8, expression of OATP-C was not significantly decreased in HCC. In transfected Huh7 cells, OATP8 promoter activity was inhibited by 70% when HNF3β was cotransfected. An HNF3β binding site was located at nt −39/−23 by EMSA. The OATP-C promoter was not inhibited by HNF3β.Conclusions: HNF3β represses transcription of the OATP8 but not the OATP-C gene, providing a mechanism for reduced expression of OATP8 in HCC. [Copyright &y& Elsevier]
- Subjects :
- *PEPTIDES
*LIVER cells
*LIVER tumors
*ELECTROPHORESIS
Subjects
Details
- Language :
- English
- ISSN :
- 01688278
- Volume :
- 40
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 11957230
- Full Text :
- https://doi.org/10.1016/j.jhep.2003.10.008