ALTERNATIVE SPLICING OF HUMAN PLASMA CHOLESTERYL ESTER TRANSFER PROTEIN MESSENGER-RNA IN CACO-2 CELLS AND ITS MODULATION BY OLEIC-ACID

Cholesteryl eater transfer protein (CETP) is a plasma protein involved in the reverse cholesterol transport and expressed in several human t issues and cell lines. We studied CETP expression in Caco-2 cell line, a model of the human enterocyte epithelium. By reverse-transcriptase polymerase chain reaction, we could demonstrate that in basal conditio n Caco-2 cells have a low rate of expression of active CETP mRNA. Furt hermore, we found that even in this cell Line CETP mRNA alternative sp licing occurs with deletion of exon 9 sequence. Densitometric analysis of the in vitro amplified fragments showed that under basal condition s about 60% of reverse transcribed CETP cDNA corresponds to exon 9-del eted transcripts. After challenge with 50 mu M sodium oleate, there is a similar to 2 fold increase in the transcription rate of the full-le ngth CETP cDNA, as measured by competitive PCR, which is accompanied t o an increased activity measured in the cell-conditioned medium. On th e contrary, no significant change is seen in the amount of exon 9-dele ted cDNA. Consequently, an inversion in the ratio of full-length and e xon 9-deleted CETP cDNA is evident, suggesting that sodium oleate sele ctively enhances the expression of full-length CETP mRNA.