Mitochondrial Uncoupling Protein 2 Expression in Colon Cancer and Its Clinical Significance

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2010 Dec 4

PMID 21128330

Citations 25

Authors

Xiao-Yi Kuai

Ze-Yu Ji

Hong-Jie Zhang

Affiliations

Soon will be listed here.

Abstract

Aim: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon cancer.

Methods: Fifteen colon tissue samples and 15 its adjacent tissue samples were obtained from colon cancer patients during surgical interventions. UCP2 expression was detected with immunohistochemical method in 10 normal controls, 10 hyperplastic polyp patients, 20 tubular adenoma patients and 78 colon cancer patients. Patients with rectal cancer were excluded. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect UCP2 expressions in colon cancer tissue samples and its adjacent tissue samples. Relation between UCP2 expression and clinical pathological features of colon cancer was also analyzed.

Results: The UCP2 mRNA expression level was four-fold higher in colon cancer tissue samples than in its adjacent tissue samples. The UCP2 protein expression level was three-fold higher in colon cancer tissue samples than in its adjacent normal tissue samples. The UCP2 was mainly expressed in cytoplasm. The UCP2 was not expressed in normal colon mucosa. Strong positive staining for UCP2 with a diffuse distribution pattern was identified throughout the mucosa in colon cancer tissue samples with a positive expression rate of 85.9%. The UCP2 expression level was higher in colon cancer tissue samples at clinical stages III and IV than in those at stage I + II. Univariate analysis showed that the high UCP2 expression level was significantly correlated to colon cancer metastasis (hazard ratio = 4.321, confidence interval = 0.035-0.682, P = 0.046).

Conclusion: UCP2 is highly expressed in human colon cancer tissue and may be involved in colon cancer metastasis.

Citing Articles

Prognostic impact and immunotherapeutic implications of NETosis-related prognostic model in clear cell renal cell carcinoma.

Mao X, Huang W, Xue Q, Zhang X J Cancer Res Clin Oncol. 2024; 150(5):278.

PMID: 38801430 PMC: 11129999. DOI: 10.1007/s00432-024-05761-y.

Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells.

Torrens-Mas M, Collado-Sole A, Sola-Leyva A, Paz Carrasco-Jimenez M, Oliver J, Pons D Biology (Basel). 2023; 12(12).

PMID: 38132283 PMC: 10740929. DOI: 10.3390/biology12121457.

Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) and Its Correlation with Immune Infiltration in Pan-Cancer.

Liu A, Liu Y, Shen S, Yan L, Lv Z, Ding H Biomed Res Int. 2022; 2022:4009354.

PMID: 36254139 PMC: 9569204. DOI: 10.1155/2022/4009354.

An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis.

Chen Y, Hong W, Liu M, Guo X, Yu Y, Cui Y Cell Death Dis. 2022; 13(3):237.

PMID: 35288533 PMC: 8921248. DOI: 10.1038/s41419-022-04692-1.

Current research progress in the role of reactive oxygen species in esophageal adenocarcinoma.

Hu Y, Ye X, Wang R, Poon K Transl Cancer Res. 2022; 10(3):1568-1577.

PMID: 35116481 PMC: 8798363. DOI: 10.21037/tcr-19-1985.

References

Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S . Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med. 2003; 9(8):1062-8. DOI: 10.1038/nm903. View

Li L, Prabhakaran K, Mills E, Borowitz J, Isom G . Enhancement of cyanide-induced mitochondrial dysfunction and cortical cell necrosis by uncoupling protein-2. Toxicol Sci. 2005; 86(1):116-24. DOI: 10.1093/toxsci/kfi164. View

Lenaz G . The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life. 2002; 52(3-5):159-64. DOI: 10.1080/15216540152845957. View

Derdak Z, Fulop P, Sabo E, Tavares R, Berthiaume E, Resnick M . Enhanced colon tumor induction in uncoupling protein-2 deficient mice is associated with NF-kappaB activation and oxidative stress. Carcinogenesis. 2006; 27(5):956-61. DOI: 10.1093/carcin/bgi335. View

Cuezva J, Krajewska M, de Heredia M, Krajewski S, Santamaria G, Kim H . The bioenergetic signature of cancer: a marker of tumor progression. Cancer Res. 2002; 62(22):6674-81. View

Harper M, Antoniou A, Villalobos-Menuey E, Russo A, Trauger R, Vendemelio M . Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J. 2002; 16(12):1550-7. DOI: 10.1096/fj.02-0541com. View

Brand M, Affourtit C, Esteves T, Green K, Lambert A, Miwa S . Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med. 2004; 37(6):755-67. DOI: 10.1016/j.freeradbiomed.2004.05.034. View

Neuzil J, Wang X, Dong L, Low P, Ralph S . Molecular mechanism of 'mitocan'-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett. 2006; 580(22):5125-9. DOI: 10.1016/j.febslet.2006.05.072. View

Derdak Z, Mark N, Beldi G, Robson S, Wands J, Baffy G . The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res. 2008; 68(8):2813-9. PMC: 2386271. DOI: 10.1158/0008-5472.CAN-08-0053. View

10.

Sreekumar A, Nyati M, Varambally S, Barrette T, Ghosh D, Lawrence T . Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001; 61(20):7585-93. View

11.

Bonnet S, Archer S, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R . A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007; 11(1):37-51. DOI: 10.1016/j.ccr.2006.10.020. View

12.

Tischoff I, Tannapfel A . [Epigenetic alterations in colorectal carcinomas and precancerous lesions]. Z Gastroenterol. 2008; 46(10):1202-6. DOI: 10.1055/s-2008-1027406. View

13.

Casteilla L, Rigoulet M, Penicaud L . Mitochondrial ROS metabolism: modulation by uncoupling proteins. IUBMB Life. 2002; 52(3-5):181-8. DOI: 10.1080/15216540152845984. View

14.

Mehta S, Li P . Neuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke. J Cereb Blood Flow Metab. 2009; 29(6):1069-78. DOI: 10.1038/jcbfm.2009.4. View

15.

Wolvetang E, Johnson K, Krauer K, Ralph S, Linnane A . Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett. 1994; 339(1-2):40-4. DOI: 10.1016/0014-5793(94)80380-3. View

16.

Collins P, Jones C, Choudhury S, Damelin L, Hodgson H . Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis. Liver Int. 2005; 25(4):880-7. DOI: 10.1111/j.1478-3231.2005.01104.x. View

17.

Boss O, Hagen T, Lowell B . Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes. 2000; 49(2):143-56. DOI: 10.2337/diabetes.49.2.143. View

18.

Teshima Y, Akao M, Jones S, Marban E . Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes. Circ Res. 2003; 93(3):192-200. DOI: 10.1161/01.RES.0000085581.60197.4D. View

19.

Horimoto M, Resnick M, Konkin T, Routhier J, Wands J, Baffy G . Expression of uncoupling protein-2 in human colon cancer. Clin Cancer Res. 2004; 10(18 Pt 1):6203-7. DOI: 10.1158/1078-0432.CCR-04-0419. View

20.

Benhar M, Engelberg D, Levitzki A . ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep. 2002; 3(5):420-5. PMC: 1084107. DOI: 10.1093/embo-reports/kvf094. View