Upregulated expression of Mina53 in cholangiocarcinoma and its clinical significance

Tan,Xiao-Ping; Zhang,Qing; Dong,Wei-Guo; Lei,Xia-Wen; Yang,Zi-Rong

doi:10.3892/ol.2012.620

Upregulated expression of Mina53 in cholangiocarcinoma and its clinical significance

Authors:
- Xiao-Ping Tan
- Qing Zhang
- Wei-Guo Dong
- Xia-Wen Lei
- Zi-Rong Yang
View Affiliations

Affiliations: Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Internal Medicine, Clinical Medical College, Yangtze University, Jingzhou, Hubei 434000, P.R. China
Published online on: February 28, 2012 https://doi.org/10.3892/ol.2012.620
Pages: 1037-1041

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

The aim of this study was to determine the level of expression of Mina53 in human cholangiocarcinoma (CCA) and to explore the role of Mina53 in carcinogenesis and tumor progression and its clinical significance in CCA. The level of expression of Mina53, p53 and Ki67 was investigated by immunohistochemistry in 69 surgically resected CCA tissues and 21 adjacent non-cancerous tissues. The correlation between Mina53 expression and clinicopathological characteristics and the expression of p53 and Ki67 was examined. Positive expression of Mina53 was observed in 61 of 69 CCA cases (88.4%) and 1 case (4.8%) of adjacent non-cancerous tissue. The level of expression of Mina53 in CCA was markedly higher than in the adjacent non-cancerous tissues. An increased level of expression of Mina53 in CCA was significantly associated with histological differentiation (P<0.01), TNM stage (P<0.05) and lymph node metastasis (P<0.01). There was no significant correlation between the level of Mina53 expression and gender, age or distant metastasis (P>0.05). However, the expression of Mina53 was associated with the expression of p53 in CCA (P<0.05). In addition, increased levels of expression of Mina53 in CCA were positively associated with Ki67 levels (r=0.801, P<0.01, as calculated by association analysis). Therefore, the upregulation of Mina53 expression may be significant in the carcinogenesis and development of human CCA and could have significant clinical value.

View Figures

View References

1	Skipworth JR, Olde Damink SW, Imber C, et al: Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer. Aliment Pharmacol Ther. 34:1063–1078. 2011. View Article : Google Scholar : PubMed/NCBI
2	Blechacz B, Komuta M, Roskams T and Gores GJ: Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 8:512–522. 2011. View Article : Google Scholar : PubMed/NCBI
3	Yamamoto M and Ariizumi S: Surgical outcomes of intrahepatic cholangiocarcinoma. Surg Today. 41:896–902. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wadsworth CA, Dixon PH, Wong JH, et al: Genetic factors in the pathogenesis of cholangiocarcinoma. Dig Dis. 29:93–97. 2011. View Article : Google Scholar : PubMed/NCBI
5	Akamatsu N, Sugawara Y and Hashimoto D: Surgical strategy for bile duct cancer: advances and current limitations. World J Clin Oncol. 2:94–107. 2011. View Article : Google Scholar : PubMed/NCBI
6	Friman S: Cholangiocarcinoma - current treatment options. Scand J Surg. 100:30–34. 2011.PubMed/NCBI
7	Tyson GL and El-Serag HB: Risk factors for cholangiocarcinoma. Hepatology. 54:173–184. 2011. View Article : Google Scholar
8	Morise Z, Sugioka A, Tokoro T, et al: Surgery and chemotherapy for intrahepatic cholangiocarcinoma. World J Hepatol. 2:58–64. 2010.PubMed/NCBI
9	Ellis MC, Cassera MA, Vetto JT, et al: Surgical treatment of intrahepatic cholangiocarcinoma: outcomes and predictive factors. HPB (Oxford). 13:59–63. 2011. View Article : Google Scholar : PubMed/NCBI
10	Fava G: Molecular mechanisms of cholangiocarcinoma. World J Gastrointest Pathophysiol. 1:12–22. 2010.
11	Lutz W, Leon J and Eilers M: Contributions of Myc to tumorigenesis. Biochim Biophys Acta. 16:61–71. 2002.
12	Dang CV: c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell. 19:1–11. 1999.PubMed/NCBI
13	Henriksson M and Luscher B: Proteins and the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res. 68:109–182. 1996. View Article : Google Scholar : PubMed/NCBI
14	Cowling VH and Cole MD: HATs off to capping: a new mechanism for Myc. Cell Cycle. 6:307–309. 2007. View Article : Google Scholar : PubMed/NCBI
15	Prochownik EV and Li Y: The ever expanding role for c-Myc in promoting genomic instability. Cell Cycle. 6:1024–1029. 2007. View Article : Google Scholar : PubMed/NCBI
16	Schick B, Wemmert S, Jung V, et al: Genetic heterogeneity of the MYC oncogene in advanced juvenile angiofibromas. Cancer Genet Cytogenet. 164:25–31. 2006. View Article : Google Scholar : PubMed/NCBI
17	Jain M, Arvanitis C, Chu K, et al: Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science. 297:102–104. 2002. View Article : Google Scholar : PubMed/NCBI
18	Tsuneoka M, Koda Y, Soejima M, et al: A novel myc target gene, mina53, that is involved in cell proliferation. J Biol Chem. 277:35450–35459. 2002. View Article : Google Scholar : PubMed/NCBI
19	Tsuneoka M, Nishimune Y, Ohta K, et al: Expression of Mina53, a product of a Myc target gene in mouse testis. Int J Androl. 29:323–330. 2006. View Article : Google Scholar : PubMed/NCBI
20	Prendergast GC: Mechanisms of apoptosis by c-Myc. Oncogene. 18:2967–2987. 1999. View Article : Google Scholar : PubMed/NCBI
21	Obaya AJ, Mateyak MK and Sedivy JM: Mysterious liaisons: the relationship between c-Myc and the cell cycle. Oncogene. 18:2934–2941. 1999. View Article : Google Scholar : PubMed/NCBI
22	Kuratomi K, Yano H, Tsuneoka M, et al: Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma. Kurume Med J. 53:71–78. 2006. View Article : Google Scholar : PubMed/NCBI
23	Tsuneoka M, Fujita H, Arima N, et al: Mina53 as a potential prognostic factor for esophageal squamous cell carcinoma. Clin Cancer Res. 10:7347–7356. 2004. View Article : Google Scholar : PubMed/NCBI
24	Teye K, Tsuneoka M, Arima N, et al: Increased expression of a Myc target gene Mina53 in human colon cancer. Am J Pathol. 164:205–216. 2004. View Article : Google Scholar : PubMed/NCBI
25	Vousden KH: P53: death star. Cell. 103:691–694. 2000. View Article : Google Scholar : PubMed/NCBI
26	Levine AJ: P53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI
27	Vogelstein B, Lane D and Levine AJ: Surfing the p53 network. Nature. 408:307–310. 2000. View Article : Google Scholar : PubMed/NCBI
28	Jiang XH, Chun YWB, Yuen ST, et al: Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3. Int J Cancer. 91:173–179. 2001. View Article : Google Scholar : PubMed/NCBI
29	Yin XY, Grove L, Datta NS, et al: C-myc overexpression and p53 loss cooperate to promote genomic instability. Oncogene. 18:1177–1184. 1999. View Article : Google Scholar : PubMed/NCBI
30	Hong S, Pusapati RV, Powers JT and Johnson DG: Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis. Cell Cycle. 5:801–803. 2006. View Article : Google Scholar : PubMed/NCBI
31	Schlüter C, Duchrow M, Wohlenberg C, et al: The cell proliferation-associated antigen of antibody Ki67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell-cycle-maintaining proteins. J Cell Biol. 123:513–522. 1993.