Browse > Article

The Relationship between the Expression of Melanoma Differentiation-Associated Gene-7/Interleukin-24 (MDA-7/IL-24) and Clinicopathological Features in Colorectal Adenocarcinomas  

Seo, Boram (Department of Pathology, Dong-A University Medical Center)
Hong, Young Seob (Department of Preventive Medicine, Dong-A University College of Medicine)
Youngmin, Youngmin (Department of Radiation Oncology, Dong-A University College of Medicine)
Roh, Mee Sook (Department of Pathology, Dong-A University College of Medicine)
Abstract
The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.
Keywords
MDA-7/IL-24; Colorectal adenocarcinoma; Immunohistochemistry; Clinicopathological feature;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Choi YM, Roh MS, Hong YS, Lee HS, Hur WJ. Interleukin-24 is correlated with differentiation and lymph node numbers in rectal cancer. World J Gastroenterol. 2011. 17: 1-7.   DOI   ScienceOn
2 American Joint Committee on Cancer. AJC cancer staging manual. 7th edition. New York: Springer; 2010.
3 Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010.
4 Chada S, Mhashilkar AM, Liu Y, Nishikawa T, Bocangel D, Zheng M, Vorburger SA, Pataer A, Swisher SG, Ramesh R, Kawase K, Meyn RE, Hunt KK. Mda-7 gene transfer sensitizes breast carcinoma cells to chemotherapy, biologic therapies and radiotherapy: correlation with expression of bcl-2 family members. Cancer Gene Ther. 2006. 13: 490-502.   DOI   ScienceOn
5 Cunningham CC, Chada S, Merritt JA, Tong A, Senzer N, Zhang Y, Mhashilkar A, Parker K, Vukelia S, Richards D, Hood J, Coffee K, Nemunaitis J. Clinical and local biological effects of and intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study. Mol Ther. 2005. 11: 149-159.   DOI
6 Fisher PB. Is mda-7/IL-24 a 'magic bullet' for cancer? Cancer Res. 2005. 65: 10128-10138.   DOI   ScienceOn
7 Dumouties L, Leemans C, Lejeune D, Kotenko SV, Renauld JC. Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol. 2001. 167: 3545-3549.   DOI
8 Ellerhorst JA, Prieto VG, Ekmekcioglu S, Broemeling L, Yekell S, Chada S, Grimm EA. Loss of MDA-7 expression with progression of melanoma. J Clin Oncol. 2002. 20: 1069-1074.   DOI   ScienceOn
9 Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990. 61: 759-767.   DOI   ScienceOn
10 Gupta P, Walter MR, Su ZZ, Lebedeva IV, Emdad L, Randolph A, Valerie K, Sarkar D, Fisher PB. BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer-specific apoptosis. Cancer Res. 2006. 66: 8182-8191.   DOI   ScienceOn
11 Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, Kang D, Jiang H, Lin JJ, Alexandre D, Chen Y, Vozhilla N, Mei MX, Christiansen KA, Sivo F, Goldstein NI, Mhashilkar AB, Chada S, Huberman E, Pestka S, Fisher PB. Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene. 2001. 48: 7051-7063.
12 Ishikawa S, Nakagawa T, Miyahara R, Kawano Y, Takenaka K, Yangihara K, Otake Y, Katakura H, Wada H, Tanaka F. Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer. Clin Cancer Res. 2005. 11: 1198-1202.
13 Jiang H, Lin JJ, Su ZZ, Goldstein NI, Fisher PB. Subtraction hybridization-identifies a novel melanoma differentiation associated gene, mda-7 modulated during human melanoma differentiation, growth and progression. Oncogene. 1995. 11: 2477-2486.
14 Jiang H, Su ZZ, Lin JJ, Goldstein NI, Young CS, Fisher PB. The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci. 1996. 9160-9165.
15 Korean National Statistical Office. 2012 annual report on the cause of death statistic. Available at http://www.kostat.go.kr/portal/korea [accessed on 11 October 2012])
16 Lebedeva IV, Su ZZ, Vozhilla N, Chatman L, Sarkar D, Dent P, Athar M, Fisher PB. Mechanism of in vitro pancreatic cancer cell growth inhibition by melanoma differentiation-associated gene-7/interleukin-24 and perillyl alcohol. Cancer Res. 2008. 68: 7439-7447.   DOI   ScienceOn
17 Lee KY. Genomic instability in colorectal cancer; from Bench to Bed. J Korean Soc Coloproctol. 2009. 25: 129-138.   DOI   ScienceOn
18 Mhashilkar AM, Schrock RD, Hindi M, Liao J, Sieger K, Kourouma F, Zou-Yang XH, Onishi E, Takh O, Vedvick TS, Fanger G, Stewart L, Watson GJ, Snary D, Fisher PB, Saeki T, Roth JA, Ramesh R, Chada S. Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy. Mol Med. 2001. 7: 271-282.   DOI
19 Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001. 2: 533-543.   DOI   ScienceOn
20 Patani N, Douglas-Jones A, Mansel R, Jian W, Mokbel K. Tumour suppressor function of MDA-7/IL-24 in human breast cancer. Cancer Cell Int. 2010. 10: 29.
21 Sauane M, Gopalkrishnan RV, Lebedeva IV, Mei MX, Sarkar D, Su ZZ, Kang DC, Dent P, Pestka S, Fisher PB. Mda-7/IL-24 induces apoptosis of diverse cancer cell lines through JAK/ STAT-independent pathways. J Cell Physiol. 2003. 196: 334-345.   DOI   ScienceOn
22 Sauane M, Lebedeva IV, Su ZZ, Choo HT, Randolph A, Valerie K, Dent P, Gopalkrishnan RV, Fisher PB. Melanoma differentiation associated gene-7/interleukin-24 promotes tumor cellspecific apoptosis through both secretory and nonsecretory pathways. Cancer Res. 2004. 64: 2988-2993.   DOI   ScienceOn
23 Su ZZ, Lebedeva IV, Sarkar D, Gopalkrishnan RV, Sauane M, Sigmon C, Yacoub A, Valerie K, Dent P, Fisher PB. Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant gliomas in a p53-independent manner. Oncogene. 2003. 22: 1164-1180.   DOI   ScienceOn
24 Su ZZ, Emdad L, Sauane M, Lebedeva IV, Sarkar D, Gupta P, James CD, Randolph A, Valerie K, Walter MR, Dent P, Fisher PB. Unique aspects of mda-7/IL-24 antitumor bystander activity: establishing a role for secretion of MDA-7/IL-24 protein by normal cells. Oncogene. 2005. 51: 7552-7566.
25 Yacoub A, Mitchell C, Brannon J, Rosenberg E, Qiao L, McKinstry R, Linehan WM, Su ZS, Sarkar D, Lebedeva IV, Valerie K, Gopalkrishnan RV, Grant S, Fisher PB, Dent PL. MDA-7 (interleukin-24) inhibits the proliferation of renal carcinoma cells and interacts with free radicals to promote cell death and loss of reproductive capacity. Mol Cancer Ther. 2003. 2: 623-632.
26 Tong AW, Nemunaitis J, Su D, Zhang Y, Cunningham C, Senzer N, Netto G, Rich D, Mhashilkar A, Parker K, Coffee K, Ramesh R, Ekmekcioglu S, Grimm EA, Van Wart Hood J, Merritt J, Chada S. Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanomadifferentiation associated gene-7 (mda-7/IL24): biologic outcome in advanced cancer patients. Mol Ther. 2005. 11: 160-172.   DOI
27 Wang CJ, Xue XB, Yi JL, Chen K, Zheng JW, Wang J, Zeng JP, Xu RH. Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2 gy replication-incompetent adenovirus vector. World J Gastroenterol. 2006. 12: 1774-1779.   DOI