Estrogen-responsive RING finger mRNA induction in gastrointestinal carcinoma cells following bile acid treatment.
The underlying molecular mechanisms of the tumor-promoting activity of bile acids such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) and the protective effect of ursodeoxycholic acid (UDCA) remain largely unclear. Using RNA arbitrarily primed PCR (RAP-PCR) for differential display, we identified, cloned and sequenced differentially expressed transcripts after treating gastric carcinoma cells (St 23132) with the bile acids CDCA, DCA and UDCA. One of these transcripts was identified to be an estrogen-responsive RING finger protein (efp) mRNA. The differential expression of efp in gastric cancer cells was confirmed by low stringency RT-PCR. efp mRNA levels were induced 3-fold in gastric carcinoma cells after CDCA and DCA treatment, whereas no change in expression was detected after UDCA treatment. Finally, treatment of the colon carcinoma cell line HT 29 with DCA resulted in a 2- to 5-fold induction of efp mRNA levels whereas UDCA did not induce efp. As expected, efp expression was also increased after 24 h of estrogen treatment. In summary, a synergy or a common pathway of tumor enhancement of bile acids and estrogen via efp in gastrointestinal carcinogenesis can be envisioned.
Jung
B
B
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Vogt
T
T
Mathieu-Daudé
F
F
Welsh
J
J
McClelland
M
M
Trenkle
T
T
Weitzel
C
C
Kullmann
F
F
D001647:Bile Acids and Salts / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005770:Gastrointestinal Neoplasms / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis*; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D016335:Zinc Fingers
D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D004967:Estrogens; D012333:RNA, Messenger; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases