Expression of Suppressor Gene Runt-Related Transcription Factor 3 in Gastric Carcinoma and Its Relationship with Clinical Pathological Parameters_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Jianhai , LI Liyi , LI Jikun

Department of General Surgery, The First Affiliated People’s Hospital of Shanghai Jiaotong University, Shanghai 200080, China;

Corresponding author：

Keywords：

Runt-related transcription factor 3; Stomach neoplasm; Suppressor gene; Pathology

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression of suppressor gene Runt-related transcription factor 3 (Runx3) in gastric carcinoma and its relationship with clinicopathologic parameters. Methods RT-PCR and Western blot were used to determine the mRNA expression and protein expression of Runx3 gene in primary tumor and corresponding normal tissues respectively in 52 patients with gastric carcinoma. The relationship between Runx3 expression and clinicopathologic parameters was analyzed. Results RT-PCR and Western blot analysis in 52 patients with gastric carcinoma showed down-regulation of Runx3 mRNA and Runx3 protein in 59.6% (31/52) and 48.1% （25/52） of the primary tumors tested, and in none of the normal tissues (P＜0.05) respectively. There was a significant negative correlation between the expression level of Runx3 gene and the clinicopathologic parameters such as tumor size, differentiation, infiltrative depth, lymph node metastasis and TNM stage (P＜0.05， P＜0.01). Runx3 gene transcription was coincident with its protein expression (r=0.840, P＜0.01）. Conclusion The expression of Runx3 gene is down-regulated in gastric carcinoma, which suggests that Runx3 gene plays an important role in carcinogenesis and the progression of gastric carcinoma. It may be a new target of diagnosis and treatment of gastric carcinoma.

Citation： ZHANG Jianhai,LI Liyi,LI Jikun. Expression of Suppressor Gene Runt-Related Transcription Factor 3 in Gastric Carcinoma and Its Relationship with Clinical Pathological Parameters. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(11): 840-843. doi: Copy

1.	Bangsow C, Rubins N, Glusman G, et al. The RUNX3 gene-sequence, structure and regulated expression [Ｊ]. Gene, 2001; 279(2)∶221.
2.	Waki T, Tamura G, Sato M, et al. Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia [Ｊ]. Cancer Sci, 2003; 94(4)∶360.
3.	Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma [Ｊ]. Lab Invest, 2004; 84(4)∶479.
4.	Miyazono K, Maeda S, Imamura T. Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins [Ｊ]. Oncogene, 2004; 23(24)∶4232.
5.	Kim WJ, Kim EJ, Jeong P, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors [Ｊ]. Cancer Res, 2005; 65(20)∶9347.
6.	Park WS, Cho YG, Kim CJ, et al. Hypermethylation of the RUNX3 gene in hepatocellular carcinoma [Ｊ]. Exp Mol Med, 2005; 37(4)∶276.
7.	Goel A, Arnold CN, Tassone P, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers [Ｊ]. Int J Cancer, 2004; 112(5)∶754.
8.	Wada M, Yazumi S, Takaishi S, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines [Ｊ]. Oncogene, 2004; 23(13)∶2401.
9.	Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma [Ｊ]. World J Gastroenterol, 2004; 10(3)∶376.
10.	Ku JL, Kang SB, Shin YK, et al. Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines [Ｊ]. Oncogene, 2004; 23(40)∶6736.
11.	Yanada M, Yaoi T, Shimada J, et al. Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines [Ｊ]. Oncol Rep, 2005; 14(4)∶817.
12.	Sato K, Tomizawa Y, Iijima H, et al. Epigenetic inactivation of the RUNX3 gene in lung cancer [Ｊ]. Oncol Rep, 2006; 15(1)∶129.
13.	Lund AH, van Lohuizen M. RUNX: a trilogy of cancer genes [Ｊ]. Cancer Cell, 2002; 1(3)∶213.
14.	Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer [Ｊ]. Cell, 2002; 109(1)∶113.
15.	Fukamachi H, Ito K. Growth regulation of gastric epithelial cells by Runx3 [Ｊ]. Oncogene, 2004; 23(24)∶4330.
16.	Otto F, Lübbert M, Stock M. Upstream and downstream targets of RUNX proteins [Ｊ]. J Cell Biochem, 2003; 89(1)∶9.
17.	Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins [Ｊ]. Nature, 1997; 390(6659)∶465.
18.	Osaki M, Moriyama M, Adachi K, et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma [Ｊ]. Eur J Clin Invest, 2004; 34(9)∶605.
19.	Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor [Ｊ]. Oncogene, 2002; 21(54)∶8351.
20.	Wei D, Gong W, Oh SC, et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis [Ｊ]. Cancer Res, 2005; 65(11)∶4809.

1. Bangsow C, Rubins N, Glusman G, et al. The RUNX3 gene-sequence, structure and regulated expression [Ｊ]. Gene, 2001; 279(2)∶221.
2. Waki T, Tamura G, Sato M, et al. Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia [Ｊ]. Cancer Sci, 2003; 94(4)∶360.
3. Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma [Ｊ]. Lab Invest, 2004; 84(4)∶479.
4. Miyazono K, Maeda S, Imamura T. Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins [Ｊ]. Oncogene, 2004; 23(24)∶4232.
5. Kim WJ, Kim EJ, Jeong P, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors [Ｊ]. Cancer Res, 2005; 65(20)∶9347.
6. Park WS, Cho YG, Kim CJ, et al. Hypermethylation of the RUNX3 gene in hepatocellular carcinoma [Ｊ]. Exp Mol Med, 2005; 37(4)∶276.
7. Goel A, Arnold CN, Tassone P, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers [Ｊ]. Int J Cancer, 2004; 112(5)∶754.
8. Wada M, Yazumi S, Takaishi S, et al. Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines [Ｊ]. Oncogene, 2004; 23(13)∶2401.
9. Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma [Ｊ]. World J Gastroenterol, 2004; 10(3)∶376.
10. Ku JL, Kang SB, Shin YK, et al. Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines [Ｊ]. Oncogene, 2004; 23(40)∶6736.
11. Yanada M, Yaoi T, Shimada J, et al. Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines [Ｊ]. Oncol Rep, 2005; 14(4)∶817.
12. Sato K, Tomizawa Y, Iijima H, et al. Epigenetic inactivation of the RUNX3 gene in lung cancer [Ｊ]. Oncol Rep, 2006; 15(1)∶129.
13. Lund AH, van Lohuizen M. RUNX: a trilogy of cancer genes [Ｊ]. Cancer Cell, 2002; 1(3)∶213.
14. Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer [Ｊ]. Cell, 2002; 109(1)∶113.
15. Fukamachi H, Ito K. Growth regulation of gastric epithelial cells by Runx3 [Ｊ]. Oncogene, 2004; 23(24)∶4330.
16. Otto F, Lübbert M, Stock M. Upstream and downstream targets of RUNX proteins [Ｊ]. J Cell Biochem, 2003; 89(1)∶9.
17. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins [Ｊ]. Nature, 1997; 390(6659)∶465.
18. Osaki M, Moriyama M, Adachi K, et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma [Ｊ]. Eur J Clin Invest, 2004; 34(9)∶605.
19. Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor [Ｊ]. Oncogene, 2002; 21(54)∶8351.
20. Wei D, Gong W, Oh SC, et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis [Ｊ]. Cancer Res, 2005; 65(11)∶4809.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Suppressor Gene Runt-Related Transcription Factor 3 in Gastric Carcinoma and Its Relationship with Clinical Pathological Parameters

Abstract Full text Figures/Tables Video References Cited by

Format

Content