The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer

Dig Dis Sci. 2004 Jun;49(6):982-9. doi: 10.1023/b:ddas.0000034558.78747.98.

Abstract

Bile acids have been implicated in the development of colorectal cancers. We investigated the expression of the transcription factor regulated by bile acids, farnesoid X receptor (FXR), as well as other components of this pathway in human colorectal tumors and cell lines. The most significant changes were a decrease in FXR mRNA levels in adenomas (5-fold average) and carcinomas (10 fold average) and an increase in peroxisome proliferator activated receptor-gamma (2-fold average). FXR was not expressed in undifferentiated colon adenocarcinoma SW480 cells and metastasis derived SW620 cells. In Caco-2 and HT-29 cells, the level of FXR expression increased with the degree of differentiation. Intestinal bile acid binding protein was activated by chenodeoxycholic acid and the synthetic FXR agonist GW4064 in Caco-2 and HT-29 but not in SW cells unless FXR was transfected. The down-regulation of the nuclear receptor FXR in colon cancer might be of clinical and pharmacological importance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adenocarcinoma / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor / metabolism
  • Colonic Neoplasms / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Liver X Receptors
  • Middle Aged
  • Orphan Nuclear Receptors
  • RNA, Messenger / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • DNA-Binding Proteins
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • farnesoid X-activated receptor
  • Hydroxysteroid Dehydrogenases
  • AKR1C2 protein, human