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Gene alterations by peroxisome proliferator-activated receptor gamma agonists in human colorectal cancer cells.

ABSTRACT: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARgamma agonists: MCC-555 (5 microM), rosiglitazone (5 microM), and 15-deoxy-Delta12,14-prostaglandin J2 (1 microM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repressed (32 genes) by tested PPARgamma agonists. These genes were analyzed by Onto-Express software and KEGG pathway analysis and revealed that PPARgamma agonists are involved in cell proliferation, focal adhesion, and several signaling pathways. Eight genes were selected to confirm the microarray data by RT-PCR and real-time PCR, from which CSTA, DAP13, TAF12, RIS1, CDKN3 and MAGOH were up-regulated, and KLHL11 and NCOA2 were down-regulated. This study elucidates the commonly induced genes modulated by tested PPARgamma ligands involved in the different signaling pathways and metabolisms, probably mediated in a PPARgamma-dependent manner in colorectal cancer cells and helps to better understand the pleiotropic actions of PPARgamma ligands.

SUBMITTER: Cekanova M

PROVIDER: S-EPMC2504864 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Gene alterations by peroxisome proliferator-activated receptor gamma agonists in human colorectal cancer cells.

Cekanova Maria M Yuan Joshua S JS Li Xiuoon X Kim Kyubo K Baek Seung Joon SJ

International journal of oncology 20080401 4

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARgamma agonists: MCC-555 (5 microM), rosiglitazone (5 microM), and 15-deoxy-Delta12,14-prostaglandin J2 (1 microM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repress ...[more]

PMID: 18360708

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Project description:BackgroundThe peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARgamma role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARgamma expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARgamma expression were also investigated in terms of K-ras mutation.MethodsPPARgamma, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique.ResultsPPARgamma expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARgamma and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples.ConclusionIn conclusion, our data demonstrated a close relationship between PPARgamma and SSAT in human colorectal cancer and this could represent an attempt to decrease polyamine levels and to reduce cell growth and tumour development. Therefore, pharmacological activation of PPARgamma and/or induction of SSAT may represent a therapeutic or preventive strategy for treating colorectal cancer.

Dataset Information

Gene alterations by peroxisome proliferator-activated receptor gamma agonists in human colorectal cancer cells.

Publications

Gene alterations by peroxisome proliferator-activated receptor gamma agonists in human colorectal cancer cells.

Similar Datasets

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