Low Expression Levels of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Gastric Cancer and its Relationship with Tumor Progression

Document Type : Original Article (s)

Authors

1 Associate Professor, Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran

2 Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

3 PhD, Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a crucial role in hindering the progression and growth of cancer cells. The function of PPARγ in gastric cancer and its relationship with progression of the disease have not been appropriately defined. Therefore, this study examined the association of PPARγ expression in tumor with advancement of gastric cancer.Methods: In the cross-sectional case-control study, the expression of PPARγ in tumoral and the paired adjacent normal tissues of 50 patients with gastric cancer, who undergone tumor resection at Institute of Imam Khomeini University Hospital, Tehran, Iran, were assayed and compared using quantitative real-time polymerase chain reaction method. Correlation between PPARγ expression in tumor tissue and the cancer progression relevant clinicopathological features was evaluated using the Spearman’s rho correlation test.Findings: The relative expression levels of PPARγ in tumoral tissues were shown to be profoundly decreased compared with their adjacent normal tissues [0.36 (0.15-0.89) vs. 1.01 (0.83-1.16), P < 0.001]. There was significant correlation between the relative expression level of PPARγ in tumoral tissues and clinicopathological features such as cancer staging, tumor differentiation, tumor size, and lymphatic and vascular invasion. However, there was no noticeable correlation between the relative PPARγ expression level and other features such as age, gender, and metastasis.Conclusion: Decreased expression of PPARγ in gastric cancer tissue compared to the adjacent normal tissues is inversely associated with the cancer progression and development relevant clinicopathological features; hence, it may play an important role in the pathophysiology of gastric cancer.

Keywords

References

  1. Han L, Shen WJ, Bittner S, Kraemer FB, Azhar S. PPARs: Regulators of metabolism and as therapeutic targets in cardiovascular disease. Part II: PPAR-beta/delta and PPAR-gamma. Future Cardiol 2017; 13(3): 279-96.
  2. Rosen ED, Spiegelman BM. PPARgamma: A nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276(41): 37731-4.
  3. Elrod HA, Sun SY. PPARgamma and apoptosis in cancer. PPAR Res 2008; 2008: 704165.
  4. Krishnan A, Nair SA, Pillai MR. Biology of PPAR gamma in cancer: A critical review on existing lacunae. Curr Mol Med 2007; 7(6): 532-40.
  5. Guo F, Ren X, Dong Y, Hu X, Xu D, Zhou H, et al. Constitutive expression of PPARgamma inhibits proliferation and migration of gastric cancer cells and down-regulates Wnt/beta-Catenin signaling pathway downstream target genes TERT and ENAH. Gene 2016; 584(1): 31-7.
  6. Kim SY, Kim MS, Lee MK, Kim JS, Yi HK, Nam SY, et al. PPARgamma induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells. Braz J Med Biol Res 2015; 48(3): 226-33.
  7. Cho SJ, Kook MC, Lee JH, Shin JY, Park J, Bae YK, et al. Peroxisome proliferator-activated receptor gamma upregulates galectin-9 and predicts prognosis in intestinal-type gastric cancer. Int J Cancer 2015; 136(4): 810-20.
  8. Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, et al. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell 1999; 3(6): 799-804.
  9. Ikezoe T, Miller CW, Kawano S, Heaney A, Williamson EA, Hisatake J, et al. Mutational analysis of the peroxisome proliferator-activated receptor gamma gene in human malignancies. Cancer Res 2001; 61(13): 5307-10.
  10. Burgermeister E, Seger R. MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma. Cell Cycle 2007; 6(13): 1539-48.
  11. Garcia-Bates TM, Lehmann GM, Simpson-Haidaris PJ, Bernstein SH, Sime PJ, Phipps RP. Role of peroxisome proliferator-activated receptor gamma and its ligands in the treatment of hematological malignancies. PPAR Res 2008; 2008: 834612.
  12. Pancione M, Forte N, Sabatino L, Tomaselli E, Parente D, Febbraro A, et al. Reduced beta-catenin and peroxisome proliferator-activated receptor-gamma expression levels are associated with colorectal cancer metastatic progression: Correlation with tumor-associated macrophages, cyclooxygenase 2, and patient outcome. Hum Pathol 2009; 40(5): 714-25.
  13. Pancione M, Sabatino L, Fucci A, Carafa V, Nebbioso A, Forte N, et al. Epigenetic silencing of peroxisome proliferator-activated receptor gamma is a biomarker for colorectal cancer progression and adverse patients' outcome. PLoS One 2010; 5(12): e14229.
  14. Ogino S, Shima K, Baba Y, Nosho K, Irahara N, Kure S, et al. Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology 2009; 136(4): 1242-50.
  15. Terashita Y, Sasaki H, Haruki N, Nishiwaki T, Ishiguro H, Shibata Y, et al. Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer. Jpn J Clin Oncol 2002; 32(7): 238-43.
  16. Yu H, Xin Y. Down-regulated expressions of PPARgamma and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren's classification in gastric carcinoma. Chin J Cancer Res 2013; 25(6): 704-14.
  17. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8.
  18. Koronowicz AA, Banks P, Master A, Domagala D, Piasna-Slupecka E, Drozdowska M, et al. Fatty Acids of CLA-Enriched Egg Yolks Can Induce Transcriptional Activation of Peroxisome Proliferator-Activated Receptors in MCF-7 Breast Cancer Cells. PPAR Res 2017; 2017: 2865283.
  19. Liu Y, Zhu ZA, Zhang SN, Mou J, Liu L, Cui T, et al. Combinational effect of PPARgamma agonist and RXR agonist on the growth of SGC7901 gastric carcinoma cells in vitro. Tumour Biol 2013; 34(4): 2409-18.
  20. Jiang Y, Zou L, Zhang C, He S, Cheng C, Xu J, et al. PPARgamma and Wnt/beta-Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations. J Cancer Res Clin Oncol 2009; 135(11): 1551-9.
Journal of Isfahan Medical School
Volume 35, Issue 440 - Serial Number 440
May and June 2017
Pages 911-918

Files

History

  • Receive Date: 19 June 2017
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics