Abstract
Abelson interactor protein-1 (ABI1) is a promising candidate tumor suppressor, and plays critical roles both in the pathogenesis of BCR-Abl-induced leukemia and in the spread of several solid tumors. The expression of ABI1 and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors, including gastric cancer. In this study, we analyzed the correlation between ABI1 expression and the clinicopathological characteristics, tumor progression, and prognosis of patients with gastric carcinoma. Tissue specimens were from 103 gastric cancer patients who underwent gastrectomy in our hospital between January 2000 and December 2007. Among them 59 tumor tissue samples were matched with normal tissue samples. The expression of ABI1 protein was measured using immunohistochemical staining of paraffin-embedded tissue specimens. Meanwhile, quantitative real-time RT-PCR and Western blotting were used to identify the expression of ABI1 in human gastric normal mucosal cell line (GES-1) and gastric cancer cell lines (N87, AGS). We performed a statistical analysis of the potential correlation between ABI1 expression and the patients’ clinicopathological characteristics, 5-year survival, and median survival time. The immunohistochemical staining results of 59 patients showed that ABI1 was expressed in 28.8% (17/59) of gastric cancer tissues, compared to 91.5% (54/59) of normal samples. ABI1 expression in 103 patients was strongly correlated with tumor differentiation, clinical stage, and lymph node status (P < 0.01). The 5-year survival rate was 15.3% in the ABI1-negative group and 63.7% in the ABI1-positive group. Median survival time in the ABI1-negative and ABI1-positive groups was 25.0 months (95% CI: 19.7–30.3) and 74.0 months (95% CI: 54.6–93.3), respectively. There was a significant difference between the two groups (χ2 = 10.888, P = 0.001). Furthermore, we found that ABI1 expressed lowly in poor differentiated AGS, whereas highly in GES-1 and well-differentiated N87. Downregulation of ABI1 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. ABI1 may be a useful diagnostic or prognostic molecular biomarker, and might be a potential target for therapeutic intervention.
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References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.
Report of the 10th annual meeting of the Chinese society of clinical oncology. 2007. http://www.heart51.com/article/2007-09-39/181191048360367.html.
Correa P. Human gastric carcinogenesis. A multistep and multifactorial process-first American Cancer Society Award Lecture on cancer epidemiology and prevention. Cancer Res. 1992;52:6735–40.
Jenei V, Jakus J. The role of EGF receptor-dependent e3B1/Abi1 protein as a tumor suppressor protein in malignant tumors. Orv Hetil. 2005;146:1293–9.
Macoska JA, Xu J, Ziemnicka D, Schwab TS, Rubin MA, Kotula L. Loss of expression of human spectrin src homology domain binding protein 1 is associated with 10p loss in human prostatic adenocarcinoma. Neoplasia. 2001;3:99–104.
Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, et al. Oncogenic abl and src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Genes Dev. 1998;12:1415–24.
Dai Z, Kerzic P, Schroeder WG, McNiece IK. Deletion of the Src homology 3 domain and C-terminal proline-rich sequences in Bcr-Abl prevents Abl interactor 2 degradation and spontaneous cell migration and impairs leukemogenesis. J Biol Chem. 2001;276:28954–60.
Funato Y, Terabayashi T, Suenaga N, Seiki M, Takenawa T, Miki H. IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness. Cancer Res. 2004;64:5237–44.
Wang C, Navab R, Iakovlev V, Leng Y, Zhang J, Tsao MS, et al. Abelson interactor protein-1 positively regulates breast cancer cell proliferation, migration, and invasion. Mol Cancer Res. 2007;5:1031–9.
Leng Y, Zhang J, Badour K, Arpaia E, Freeman S, Cheung P, et al. Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation. Proc Natl Acad Sci USA. 2005;102:1098–103.
Stuart JR, Gonzalez FH, Kawai H, Yuan ZM. c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading. J Biol Chem. 2006;281:31290–7.
Gu Y, Souza RF, Wu RF, Xu YC, Terada LS. Induction of colonic epithelial cell apoptosis by p47-dependent oxidants. FEBS Lett. 2003;540:195–200.
Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of digestive system. In: Hamilton SR, Aaltonen LA, editors. WHO classification of tumors. Lyon: IARC Press; 2000. p. 38.
Mullaney PJ, Wadley MS, Hyde C, Wyatt J, Lawrence G, Hallissey MT, et al. Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Union Internacional Contra la Cancrum/American Joint Committee on Cancer. Br J Surg. 2002;89:1405–8.
Shi Y, Alin K, Goff SP. Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses w-abl transforming activity. Genes Dev. 1995;9:2583–97.
Noske A, Denkert C, Schober H, Sers C, Zhumabayeva B, Weichert W, et al. Loss of Gelsolin expression in human ovarian carcinomas. Eur J Cancer. 2005;41:461–9.
Weichert W, Roske A, Niesporek S, Noske S, Buckendahl AC, Dietel M, et al. Class histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14:1669–77.
Hamm A, Veeck J, Bektas N, Wild P, Hartmann A, Heindrichs U, et al. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: a systematic expression analysis. BMC Cancer. 2008;8:25 (on line).
Ke Y, Ning T, Wang B. Establishment and characterization of a SV40 transformed human fetal gastric epithelial cell line-GES-1. Zhonghua Zhong Liu Za Zhi. 1994;16:7–10.
Morerio C, Rosanda C, Rapella A, Micalizzi C, Panarello C. Is t(10; 11)(p11.2;q23) involving MLL and ABI1 genes associated with congenital acute monocytic leukemia? Cancer Genet Cytogenet. 2002;139:57–9.
Stradal TE, Scita G. Complexes regulating Arp2/3-mediated actin assembly. Curr Opin Cell Biol. 2006;18:4–10.
Oliveira FJ, Ferrao H, Furtado E, Batista H, Conceicao L. Early gastric cancer: report of 58 cases. Gastric Cancer. 1998;1:51–6.
Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: fifth edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer. 2000;88:921–32.
Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51:15–36.
Hejna M, Wohrer S, Schmidinger M, Raderer M. Postoperative chemotherapy for gastric cancer. Oncologist. 2006;11:136–45.
Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell. 2003;112:453–65.
Rao J, Li N. Microfilament actin remodeling as a potential target for cancer drug development. Curr Cancer Drug Targets. 2004;4:345–54.
Yu W, Sun X, Clough N, Cobos E, Tao Y, Dai Z. ABI1 gene silencing by short hairpin RNA impairs Bcr-Abl-induced cell adhesion and migration in vitro and leukemogenesis in vivo. Carcinogenesis. 2008;29:1717–24.
Biesova Z, Piccoli C, Wong WT. Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth. Oncogene. 1997;14:233–41.
Jenei V, Andersson T, Jakus J, Dib K. E3B1, a human homologue of the mouse gene product ABI1, sensitizes activation of Rap1 in response to epidermal growth factor. Exp Cell Res. 2005;310:463–73.
Ikeguchi A, Yang HY, Gao G, Goff SP. Inhibition of v-abl transformation in 3T3 cells overexpressing different forms of the abelson interactor protein ABI1. Oncogene. 2001;20:4926–34.
Fan PD, Goff SP. Abl interactor 1 binds to sos and inhibits epidermal growth factor- and v-abl-induced activation of extracellular signal-regulated kinases. Mol Cell Biol. 2000;20:7591–601.
Acknowledgments
We are grateful to Dr. Qiang Gao (Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, USA) for expert help in the preparation and revision comments of this manuscript. This study was supported by a grant from the Peking University People’s Hospital Research and Development Foundation (RDB2008-06).
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M. Cui and W Yu contributed equally to this study.
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Cui, M., Yu, W., Dong, J. et al. Downregulation of ABI1 expression affects the progression and prognosis of human gastric carcinoma. Med Oncol 27, 632–639 (2010). https://doi.org/10.1007/s12032-009-9260-6
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DOI: https://doi.org/10.1007/s12032-009-9260-6