Expression of peroxisome proliferator‐activated receptors alpha and gamma in differentiating human colon carcinoma Caco‐2 cells

Huin, Cécile; Schohn, Hervé; Hatier, R; Bentéjac, Marc; Antunes, Laurent; Plénat, François; Bugaut, Maurice; Dauça, Michel

doi:10.1016/s0248-4900(01)01178-9

Cited by 25 publications

(20 citation statements)

References 68 publications

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“…HT-29 and HCT116 cells remained undifferentiated in the same culture delay. As previously shown (26), catalase content used as a marker of differentiation was increased during spontaneous differentiation process occurring in Caco-2 cells, but also in HT-29 MTX 10 -5 M Rev cells. We demonstrated that PPARÁ protein was present in these cells with an estimated Mr at 50 kDa (Fig.…”

Section: Presence Of Ppará Protein In Colon Derivedsupporting

confidence: 72%

Genetic analysis of peroxisome proliferator-activated receptor γ1 splice variants in human colorectal cell lines

Fiatte

Huin²,

Bertin³

et al. 2006

Int J Oncol

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Abstract. Peroxisome proliferator-activated receptor Á (PPARÁ) is a member of the nuclear hormone receptor family. In colon, this transcription factor is involved in differentiation of absorptive cells. PPARÁ participates also in colon carcinogenesis and cancer progression. Two isoforms, namely PPARÁ1 and PPARÁ2, have been described. Recently, new PPARÁ1 transcripts whose translation raises PPARÁ1 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 PPARÁ 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 PPARÁ transcripts from colon-derived cell lines or in those derived from other tissue. Using HT-29 cells, changes in PPARÁ1 mRNA levels were observed after treatment with PPARÁ agonists such as pioglitazone and troglitazone. These modifications correlated with particular PPARÁ transcripts excluding the untranslated exon A2. HT-29 cells treatment with actinomycin D or cycloheximide showed that the presence of PPARÁ mRNA including exon A2 was dependent on de novo protein synthesis. We concluded that diverse PPARÁ1 mRNA exist in colorectal cells. Levels of PPARÁ1 transcript varied according to the phenotype of colon cell model used. We suggest that regulation of PPARÁ1 mRNA levels could be dependent in part on the composition of untranslated exon(s) in the 5' UTR of PPARÁ1 mRNA. IntroductionPeroxisome proliferator activated receptors (PPAR) belong to the nuclear hormone receptor superfamily (1). There are three isotypes named PPAR·, PPARß/‰ and PPARÁ (2). These nuclear receptors act as heterodimers with the 9-cis retinoic acid receptor and bind to a specific DNA sequence, the peroxisome proliferator response element, a direct repeat of the 5'-AGGTCA-3' sequence spaced by one base (3,4). After ligand activation, the heterodimer complex regulates the transcription of specific genes involved in several physiological functions (2). In colon, PPARÁ is implicated in differentiation of absorptive cells (5), in carcinogenesis or tumour progression even though contradictory results have been obtained in murine and human models (6).The PPARÁ gene is localised to chromosome 3, band 3p25 (7). The open reading frame consists of exons E1-E6 which encode the different domains of the protein. In human, two PPARÁ isoforms have been identified and referred to as PPARÁ1 and PPARÁ2 (7,8). PPARÁ2 differs from PPARÁ1 by an additional 28 amino acid NH2-terminal sequence (8). The 5' UTR region of PPARÁ transcripts, raising PPARÁ1 and -2 proteins, is highly variable and three exons termed A1, A2 and B have been described (9,10). Due to different promoter usage and alternative splicing, two other PPARÁ transcripts have been identified and they have been referred to as PPARÁ3 and -Á4 (10,11). PPARÁ1 mRNA consists of A...

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Section: Presence Of Ppará Protein In Colon Derivedsupporting

confidence: 72%

Genetic analysis of peroxisome proliferator-activated receptor γ1 splice variants in human colorectal cell lines

Fiatte

Huin²,

Bertin³

et al. 2006

Int J Oncol

Self Cite

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“…The importance of PPARg in the colon is implied by variation of expression of PPARg within the distal and proximal colon (1,2) as well as by increased levels in more differentiated epithelial cells (1,(3)(4)(5)(6). Free fatty acids are known to bind to PPARg with polyunsaturated fatty acids having the higher binding affinity than saturated or monounsaturated fatty acids (7,8) and with greater activation stemming from oxidized polyunsaturated fatty acids than unoxidized fatty acids (9).…”

Section: Introductionmentioning

confidence: 99%

Interactions of Peroxisome Proliferator–Activated Receptor γ and Diet in Etiology of Colorectal Cancer

Murtaugh¹,

Ni²,

Caan

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The peroxisome proliferator -activated receptor ; (PPAR;) is one of a group of ligand-activated nuclear receptors responsible for regulation of glucose, lipid homeostasis, cell differentiation, and apoptosis. The 12 proline-to-alanine (Pro12Ala) substitution polymorphism in PPARg produces proteins with lower activity. Variation in PPARg expression in the bowel and the role of dietary fatty acids as ligands for PPAR; led investigation of whether the associations of diet with colon and rectal cancer risk were modified by PPARg genotype. Data (diet, lifestyle, and DNA) came from casecontrol studies of colon (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake, dietary fiber, and calcium. We found no significant interactions between macronutrient (fat, protein, and carbohydrate) and colorectal cancer. High lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA PPARg genotype were associated with reduced colon cancer risk. Risk of rectal cancer was increased among those with the PA/AA PPARg genotype and a high mutagen index (OR, 1.63; 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for PPARg is related to activation of PPAR; by nutrients or dietary patterns acting as ligands or direct influences of these nutrients on colon and rectal cancer processes that are important with lower PPAR; activity.

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“…Among PPARs, PPARg is primarily expressed in adipose tissue and is an important regulator of adipocyte differentiation (Lowell, 1999). Recent studies have demonstrated the presence of PPARg in colon, prostate, bladder, breast, and other human cancer cells (Elstner et al, 1998;Kubota et al, 1998;Mueller et al, 1998;Sarraf et al, 1998;Chang and Szabo, 2000;Huin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

et al. 2004

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We previously reported that the PPARc agonist troglitazone (TRO) inhibits proliferation and induces apoptosis in human MCF-7 breast carcinoma cells. To understand the mechanisms of antiproliferative and pro-apoptotic effects of TRO, we screened a limited DNA array containing 23 genes involved in regulating either the cell cycle and/or apoptosis. Four of the 23 genes screened exhibited regulation by TRO, with growth arrest and DNA damage-inducible gene 45 (GADD45) being the most strongly upregulated. TRO induced GADD45 mRNA expression in a time-and dose-dependent manner. Depletion of GADD45 by siRNA abrogated TROinduced apoptosis in MCF-7 cells demonstrating the physiological relevance of GADD45 upregulation. Signaling pathways mediating TRO-induced GADD45 were also investigated. Several mitogen-activated protein kinase (MAPK) pathways were involved in the induction of GADD45 by TRO. Inhibition of the c-jun N-terminal kinase MAPK pathway by SP600125 partially abolished TRO-induced GADD45 mRNA, and protein expression and apoptosis. In contrast, inhibition of the p38 MAPK pathway by SB203580, or through overexpression of a dominant-negative mutant of p38 MAPK, augmented GADD45 mRNA induction and GADD45 promoter activation as well as cell apoptosis by TRO. Blockade of the extracellular signal-regulated kinase MAPK pathway by PD98059 also enhanced TRO's effects on GADD45 and apoptosis. Two other PPARc agonists pioglitazone and rosiglitazone did not induce GADD45 expression. Our finding of GADD45 induction by TRO may provide a new insight concerning the mechanisms for TRO's antiproliferative and pro-apoptotic effects in breast cancer cells.

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Expression of peroxisome proliferator‐activated receptors alpha and gamma in differentiating human colon carcinoma Caco‐2 cells

Cited by 25 publications

References 68 publications

Genetic analysis of peroxisome proliferator-activated receptor γ1 splice variants in human colorectal cell lines

Genetic analysis of peroxisome proliferator-activated receptor γ1 splice variants in human colorectal cell lines

Interactions of Peroxisome Proliferator–Activated Receptor γ and Diet in Etiology of Colorectal Cancer

Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells

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