Fiatte Cathy, Huin Cécile, Bertin Isabelle, Lesuffleur Thécla, Pluvinet Arnaud, Touche Nadège, Plénat François, Dauça Michel, Domenjoud Lionel, Schohn Hervé
EA 3446 Proliférateurs de Peroxysomes, Laboratoire de Biologie Cellulaire du Développement, Faculté des Sciences et Techniques, 54506 Vandoeuvre les Nancy Cedex, France.
Int J Oncol. 2006 Dec;29(6):1601-10.
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.
过氧化物酶体增殖物激活受体γ（PPARγ）是核激素受体家族的成员。在结肠中，这种转录因子参与吸收细胞的分化。PPARγ也参与结肠癌的发生和癌症进展。已描述了两种亚型，即PPARγ1和PPARγ2。最近，已对新的PPARγ1转录本进行了表征，其翻译可提高PPARγ1蛋白水平。它们因位于PPARG基因5'UTR中的非翻译外显子的组合而彼此不同。在此，我们研究了在人结肠细胞模型中是否存在这种PPARγ转录本的多样性。基于生物信息学分析，在人PPARG基因中鉴定出推定的非翻译外显子。通过RT-PCR分析，我们证明这些非翻译外显子中的几个包含在来自结肠来源的细胞系或其他组织来源的细胞系的PPARγ转录本中。使用HT-29细胞，在用吡格列酮和曲格列酮等PPARγ激动剂处理后，观察到PPARγ1 mRNA水平的变化。这些修饰与排除非翻译外显子A2的特定PPARγ转录本相关。用放线菌素D或环己酰亚胺处理HT-29细胞表明，包含外显子A2的PPARγ mRNA的存在依赖于从头蛋白质合成。我们得出结论，在结直肠细胞中存在多种PPARγ1 mRNA。PPARγ1转录本的水平根据所用结肠细胞模型的表型而变化。我们认为，PPARγ1 mRNA水平的调节可能部分取决于PPARγ1 mRNA 5'UTR中非翻译外显子的组成。
