Effect of peroxisome proliferator activated receptor   ligands on growth and gene expression profiles of gastric cancer cells

Leung, Wai K.; Bai, Alfa H.C.; Chan, Vny; Yu, Jie; Chan, Michael W.Y.; To, KF; Wu, J-R; Chan, KK; Fu, Y-G; Chan, Francis K.L.; Sung, Joseph J.Y.

doi:10.1136/gut.2003.021105

Cited by 65 publications

(46 citation statements)

References 35 publications

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“…PPARg, activated by statins (32), suppresses proinflammation gene expression (42). This study showed that pitavastatin treatment decreased serum leptin levels and increased PPARg activity in the intestinal mucosa and the liver.…”

Section: Discussionmentioning

confidence: 79%

Inhibition of Intestinal Polyp Formation by Pitavastatin, a HMG-CoA Reductase Inhibitor

Teraoka

Mutoh

Takasu

et al. 2011

Cancer Prevention Research

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It has been suggested that hyperlipidemia is positively associated with colon carcinogenesis. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, reduce serum lipid levels. In this study, we clarified the effects of a novel chemically synthesized statin, pitavastatin, on intestinal polyp formation in Min mice, and further examined serum lipid and adipocytokine levels, and proinflammatory and adipocytokine gene levels in intestinal mucosa of Min mice. Treatment with pitavastatin at doses of 20 and 40 ppm decreased the total number of polyps dose-dependently to 85.2% and 65.8% (P < 0.05) of the untreated value, respectively. Serum levels of total cholesterol and triglyceride were slightly reduced and those of IL-6, leptin, and MCP-1 were decreased by 40-ppm pitavastatin treatment. mRNA expression levels of cyclooxygenase-2, IL-6, inducible nitric oxide (iNOS), MCP-1, and Pai-1 were significantly reduced in intestinal nonpolyp parts by pitavastatin treatment. Among them, iNOS mRNA levels were also reduced in the intestinal polyps. Moreover, oxidative stress represented by 8-nitroguanosine in the small intestinal epithelial cells was reduced by pitavastatin treatment. Related to these proinflammatory genes, PPARg activity was activated in the intestinal nonpolyp parts and in the liver of Min mice with pitavastatin treatment. These results indicated that pitavastatin has potential benefit for the suppression of intestinal polyp development. Cancer Prev Res; 4(3); 445-53. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 79%

Inhibition of Intestinal Polyp Formation by Pitavastatin, a HMG-CoA Reductase Inhibitor

Teraoka

Mutoh

Takasu

et al. 2011

Cancer Prevention Research

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“…In addition, PPARg ligands have been shown to inhibit transcriptional activation of COX-2 in human epithelial cells (Badawi et al, 2004). In certain cancer cells, ligand activation of PPARg results in the inhibition of the release of inflammatory cytokines by cancer cells (Leung et al, 2004). These results may help to explain the shuttling of PPARg expression from the cytoplasm to nucleus with the progression of ovarian carcinoma.…”

Section: Discussionmentioning

confidence: 83%

“…In another study, loss of PPARg was shown not to affect mammary development and propensity for tumour formation but resulted in reduced fertility (Cui et al, 2002). Overall, ligand activation of PPARg in tumour models can result in diversified functional outcome (Leung et al, 2004) and a better understanding of the exact role of PPARg in cancer needs to be determined. In particular, the mechanism of differentiation of cancers is incompletely understood and an insight into this process would undoubtedly lead to new therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma

et al. 2004

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The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARg in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARg in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARg was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARg expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARg expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARg was observed in high-grade ovarian tumours with PPARg being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARg immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (w 2 ¼ 48.80, Po0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARg in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (Po0.01). These findings suggest an involvement of PPARg in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

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“…Ligand binding to PPAR activates the transcription of PPAR responsive genes including cellular development, differentiation and carcinogenesis. PPARγ gene expression was identified in both gastric cancerous and normal gastric epithelium (Leung et al, 2004). It has also been shown activation of PPARγ inhibits the growth and induces apoptosis of gastric cancer cells (Leung et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

PPAR-Gamma Pro12Ala Polymorphism and Gastric Cancer Risk in a Turkish Population

Canbay

Kurnaz²,

Canbay³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the PPARγ Pro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). Patients and Methods: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of PPARγ Pro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The Ala12 allele of the PPARγ Pro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. Conclusion: This study suggests that the PPARγ Pro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the PPARγ Pro12Ala polymorphism in GC.

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Effect of peroxisome proliferator activated receptor ligands on growth and gene expression profiles of gastric cancer cells

Cited by 65 publications

References 35 publications

Inhibition of Intestinal Polyp Formation by Pitavastatin, a HMG-CoA Reductase Inhibitor

Inhibition of Intestinal Polyp Formation by Pitavastatin, a HMG-CoA Reductase Inhibitor

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma

PPAR-Gamma Pro12Ala Polymorphism and Gastric Cancer Risk in a Turkish Population

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