The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma

J Hepatol. 2004 Feb;40(2):212-8. doi: 10.1016/j.jhep.2003.10.008.


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 3beta (HNF3beta) 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 HNF3beta was cotransfected. An HNF3beta binding site was located at nt -39/-23 by EMSA. The OATP-C promoter was not inhibited by HNF3beta.

Conclusions: HNF3beta represses transcription of the OATP8 but not the OATP-C gene, providing a mechanism for reduced expression of OATP8 in HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / physiopathology*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 3-beta
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / physiopathology*
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Organic Anion Transporters, Sodium-Independent / genetics*
  • Promoter Regions, Genetic
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Transcription Factors / genetics*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • FOXA2 protein, human
  • Liver-Specific Organic Anion Transporter 1
  • Nuclear Proteins
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta