Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology

Lin,Mao Song; Huang,Jun Xing; Chen,Wei Chang; Zhang,Bao Feng; Fang,Jing; Zhou,Qiong; Hu,Ying; Gao,Heng Jun

doi:10.3892/ol.2011.414

Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology

Authors:
- Mao Song Lin
- Jun Xing Huang
- Wei Chang Chen
- Bao Feng Zhang
- Jing Fang
- Qiong Zhou
- Ying Hu
- Heng Jun Gao
View Affiliations

Affiliations: Department of Gastroenterology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Department of Gastroenterology, the First Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215006, P.R. China, National Engineering Center for Biochip at Shanghai, Tongji Hospital Affiliated to Tongji University, Shanghai 201203, P.R. China
Published online on: September 6, 2011 https://doi.org/10.3892/ol.2011.414
Pages: 1219-1224

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin‑embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

View Figures

View References

1	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer Statistics 2009. CA Cancer J Clin. 59:1–25. 2009. View Article : Google Scholar
2	Hung KE and Chung DC: New insights into the molecular pathogenesis of colorectal cancer. Drug Discov Today Dis Mech. 3:439–445. 2006. View Article : Google Scholar : PubMed/NCBI
3	Glass CK and Rosenfeld MG: The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14:121–141. 2000.PubMed/NCBI
4	Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM and Lehmann JM: Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. PNAS. 94:4318–4323. 1997. View Article : Google Scholar
5	Matthiessen MW, Pedersen G, Albrektsen T, Adamsen S, Fleckner J and Brynskov J: Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas. Scand J Gastroenterol. 40:198–205. 2005. View Article : Google Scholar
6	Su WD, Bush CR, Necela BM, Calcagno SR, Murray NR, Fields AP and Thompson EA: Differential expression, distribution, and function of PPARγ in the proximal and distal colon. Physiol Genomics. 30:342–353. 2007.
7	Schwab M, Reynders V, Loitsch S, Shastri YM, Steinhilber D, Schröder O and Stein J: PPARγ is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells. Carcinogenesis. 29:1407–1414. 2008.
8	Eng C: PTEN: one gene, many syndromes. Hum Mutat. 22:183–198. 2003. View Article : Google Scholar : PubMed/NCBI
9	Nassif NT, Lobo GP, Wu X, Henderson CJ, Morrison CD, Eng C, Jalaludin B and Segelov E: PTEN mutations are common in sporadic microsatellite stable colorectal cancer. Oncogene. 23:617–628. 2004. View Article : Google Scholar : PubMed/NCBI
10	Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J and Pandolfi PP: The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 455:813–817. 2008. View Article : Google Scholar : PubMed/NCBI
11	Lobo GP, Waite KA, Planchon SM, Romigh T, Nassif NT and Eng C: Germline and somatic cancer-associated mutations in the ATP-binding motifs of PTEN influence its subcellular localization and tumor suppressive function. Hum Mol Genet. 18:2851–2862. 2009. View Article : Google Scholar : PubMed/NCBI
12	Rahman MA, Dhar DK, Yamagicgi E, Maruyama S, Sato T, Hayashi H, Ono T, Yamanoi A, Kohno H and Nagasue N: Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases. Clin Cancer Res. 7:1325–1332. 2001.
13	Nagata D, Yoshihiro H, Nakanishi M, Naruyama H, Okada S, Ando R, Tozawa K and Kohri K: Peroxisome proliferator-activated receptor-gamma and growth inhibition by its ligands in prostate cancer. Cancer Detect Prev. 32:259–66. 2008. View Article : Google Scholar : PubMed/NCBI
14	Sato H, Ishihara S, Kawashima K, Moriyama N, Suetsugu H, Kazumori H, Okuyama T, Rumi MA, Fukuda R, Nagasue N and Kinoshita Y: Expression of peroxisome proliferator-activated receptor (PPAR) γ in gastric cancer and inhibitory effects of PPARγ agonists. Br J Cancer. 83:1394–1400. 2000.
15	Sun WH, Chen GS, Ou XL, Yang Y, Luo C, Zhang Y, Shao Y, Xu HC, Xiao B, Xue YP, et al: Inhibition of COX-2 and activation of peroxisome proliferator-activated receptor gamma synergistically inhibits proliferation and induces apoptosis of human pancreatic carcinoma cells. Cancer Lett. 275:247–255. 2009. View Article : Google Scholar
16	Chen D, Jin GF, Wang Y, Wang H, Liu H, Liu Y, Fan W, Ma H, Miao R, Hu Z, et al: Genetic variants in peroxisome proliferator-activated receptor-γ gene are associated with risk of lung cancer in a Chinese population. Carcinogenesis. 29:342–350. 2008.
17	Mansen A, Guardiola-Diaz H, Rafter J, Branting C and Gustafsson JA: Expression of the peroxisome proliferators-activated receptor (PPAR) in the mouce colonic mucosa. Biochem Biophys Res Commun. 222:844–851. 1996. View Article : Google Scholar : PubMed/NCBI
18	Fujisawa T, Nakajima A, Fujisawa N, Takahashi H, Ikeda I, Tomimoto A, Yonemitsu K, Nakajima N, Kudo C, Wada K, et al: Peroxisome proliferator-activated receptor gamma (PPARgamma) suppresses colonic epithelial cell turnover and colon carcinogenesis through inhibition of the beta-catenin/T cell factor (TCF) pathway. J Pharmacol Sci. 106:627–38. 2008. View Article : Google Scholar
19	Eun CS, Han DS, Lee SH, Paik CH, Chung YW, Lee J and Hahm JS: Attenuation of colonic inflammation by PPARγ in intestinal epithelial cells: effect on toll-like receptor pathway. Dig Dis Sci. 51:693–697. 2006.
20	Feilchenfeldt J, Brundler MA, Soravia C, Totsch M and Meier CA: Peroxisome proliferators-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1). Cancer Lett. 203:25–33. 2004. View Article : Google Scholar
21	Hisatake J, Ikezoe T, Carey M, Holden S, Tomoyasu S and Koeffler HP: Down-regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma (troglitazone) in human prostate cancer. Cancer Res. 19:5494–5498. 2000.
22	Puzio-Kuter AM, Martin MC, Kinkade CW, Wang X, Shen TH, Matos T, Shen MM, Cordon-Cardo C and Abate-Shen C: Inactivation of p53 and Pten promotes invasive bladder cancer. Genes and Dev. 23:675–680. 2009. View Article : Google Scholar : PubMed/NCBI
23	Iwanaga K, Yang YN, Raso MG, Ma L, Hanna AE, Thilaganathan N, Moghaddam S, Evans CM, Li H, Cai WW, et al: Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. Cancer Res. 68:1119–1127. 2008. View Article : Google Scholar : PubMed/NCBI
24	Loupakis F, Pollina L, Stasi I, Ruzzo A, Scartozzi M, Santini D, Masi G, Graziano F, Cremolini C, Rulli E, et al: PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol. 27:2622–2629. 2009. View Article : Google Scholar : PubMed/NCBI
25	Zhou XP, Loukola A, Salovaara R, Nystrom-Lahti M, Peltomaki P, De la Chapelle A, Aaltonen LA and Eng C: PTEN mutational spectra expression levels and subcellular localization in microsatellite stable and unstable colorectal cancers. Am J Pathol. 161:439–447. 2002. View Article : Google Scholar : PubMed/NCBI
26	Lobo GP, Waite KA, Planchon SM, Romigh T, Houghton JA and Eng C: ATP modulates PTEN subcellular localization in multiple cancer cell lines. Hum Mol Genet. 17:2877–2885. 2008. View Article : Google Scholar : PubMed/NCBI
27	Bowen KA, Doan HQ, Zhou BP, Wang Q, Zhu Y, Rychahou PG and Evers BM: PTEN loss induces epithelial-mesenchymal transition in human colon cancer cells. Anticancer Res. 29:4439–4449. 2009.PubMed/NCBI
28	Rychahou PG, Kang JH, Gulhati P, Doan HQ, Chen LA, Xiao SY, Chung DH and Evers BM: Akt2 over expression plays a critical role in the establishment of colorectal cancer metastasis. PNAS. 105:20315–20320. 2008. View Article : Google Scholar : PubMed/NCBI