ESTROGEN-RESPONSIVE RING FINGER MESSENGER-RNA 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 differ ential display, we identified, cloned and sequenced differentially exp ressed transcripts after treating gastric carcinoma cells (St 23132) w ith the bile acids CDCA, DCA and UDCA, One of these transcripts was id entified to be an estrogen-responsive RING finger protein (efp) mRNA, The differential expression of efp in gastric cancer cells was confirm ed by low stringency RT-PCR, efp mRNA levels were induced 3-fold in ga stric 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-fo ld induction of efp mRNA levels whereas UDCA did not induce efp, As ex pected, efp expression was also increased after 24 h of estrogen treat ment, In summary, a synergy or a common pathway of tumor enhancement o f bile acids and estrogen via efp in gastrointestinal carcinogenesis c an be envisioned.