Genetic analysis of peroxisome proliferator-activated receptor gamma1 splice variants in human colorectal cell lines.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor family. In colon, this transcription factor is involved in differentiation of absorptive cells. PPARgamma participates also in colon carcinogenesis and cancer progression. Two isoforms, namely PPARgamma1 and PPARgamma2, have been described. Recently, new PPARgamma1 transcripts whose translation raises PPARgamma1 protein have been characterised. They differ from each other by combination of untranslated exons localised in the 5' UTR of the PPARG gene. Here, we studied whether such a diversity of PPARgamma transcripts occurs in human colon cell models. Based on bioinformatic analysis, putative untranslated exons were identified in the human PPARG gene. By RT-PCR analysis, we have demonstrated that several of these untranslated exons are included in PPARgamma transcripts from colon-derived cell lines or in those derived from other tissue. Using HT-29 cells, changes in PPARgamma1 mRNA levels were observed after treatment with PPARgamma agonists such as pioglitazone and troglitazone. These modifications correlated with particular PPARgamma transcripts excluding the untranslated exon A2. HT-29 cells treatment with actinomycin D or cycloheximide showed that the presence of PPARgamma mRNA including exon A2 was dependent on de novo protein synthesis. We concluded that diverse PPARgamma1 mRNA exist in colorectal cells. Levels of PPARgamma1 transcript varied according to the phenotype of colon cell model used. We suggest that regulation of PPARgamma1 mRNA levels could be dependent in part on the composition of untranslated exon(s) in the 5' UTR of PPARgamma1 mRNA.
Fiatte
Cathy
C
EA 3446 Proliférateurs de Peroxysomes, Laboratoire de Biologie Cellulaire du Développement, Faculté des Sciences et Techniques, 54506 Vandoeuvre les Nancy Cedex, France.
Huin
Cécile
C
Bertin
Isabelle
I
Lesuffleur
Thécla
T
Pluvinet
Arnaud
A
Touche
Nadège
N
Plénat
François
F
Dauça
Michel
M
Domenjoud
Lionel
L
Schohn
Hervé
H
D001483:Base Sequence; D018938:Caco-2 Cells; D002839:Chromans / Q000494:pharmacology; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005091:Exons; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D000077205:Pioglitazone; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D020506:Untranslated Regions
D002839:Chromans; D047495:PPAR gamma; D020033:Protein Isoforms; D012333:RNA, Messenger; D045162:Thiazolidinediones; D020506:Untranslated Regions; D003609:Dactinomycin; D003513:Cycloheximide; D000077288:Troglitazone; D000077205:Pioglitazone