Expressions and Clinical Significance of PTEN, Fas/FasL and MMP-2 in Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Peng , GUO Lin , WANG Qiang

*Department of Gastroduodenal General Surgery，Shengjing Hospital of China Medical University, Shenyang 110004, China;

Corresponding author：

Keywords：

Phosphatase and tensin homolog deleted on chromosome ten; Fas/FasL system; Matrix metalloproteinases-2; Gastric cancer; Immunohistochemistry

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Objective To study the expressions of phosphatese and tensin homolog deletedin chromosom ten （PTEN）, Fas/FasL system and matrix metalloproteinnases-2 （MMP-2） in human gastric cancer. Methods Seventy-five cases of gastric carcinoma were selected from paraffin wax embodied specimens with full clinicopathological data, and another 15 cases of normal gastric mucosa specimens were selected as the control group. SP immunohistochemistry was used to measure the expressions of PTEN， Fas/FasL and MMP-2 in them. The data was statistically analyzed by χ2 test and relative analysis. Results The expressions of PTEN, Fas/FasL and MMP-2 were correlated with the lymphatic metastasis, degree of infiltration, clinical TMN stage and pathological histological differentiated degree of gastric cancer (P lt;0.05). PTEN was positive correlated with Fas/FasL (r=0.401, P lt;0.001). MMP-2 was negative correlated with Fas/FasL (r=－0.720， P lt;0.001). MMP-2 was negative correlated with PTEN (r=－0.336， P lt;0.001). Conclusion There is guidance meaning in testing the expressions of PTEN, Fas/FasL and MMP-2 in gastric cancer to estimate the prevention, diagnoses, therapy and prognosis of gastric cancer.

Citation： WANG Peng,GUO Lin,WANG Qiang. Expressions and Clinical Significance of PTEN, Fas/FasL and MMP-2 in Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(12): 991-995. doi: Copy

1.	Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [J]. Science, 1997； 275(5308): 1943-1947.
2.	Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta [J]. Cancer Res, 1997； 57 (11): 2124-2129.
3.	Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumor suppressor gene MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers [J]. Nat Genet, 1997； 15(4): 356-362.
4.	熊敏, 吴一龙主编. 现代肺癌病理与临床 [M]. 北京：北京科学出版社，2003: 97-98.
5.	Zhao MD, Hu XM, Sun DJ, et al. Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma [J]. World J Gastroenterol, 2005； 11 (21): 3217-3221.
6.	Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas [J]. Br J Cancer, 1999； 79 (11-12): 1828-1835.
7.	Yoo CH, Noh SH, Kim YI, et al. Comparison of prognostic significance of nodal staging between old (4th edition) and new (5th edition) UICC TNM classification for gastric carcinoma. International Union Against Cancer [J]. World J Surg, 1999; 23(5): 492-497.
8.	Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival [J]. Gastroenterology， 1997; 112(1): 46-54.
9.	陈昊, 李玉民, 何明彦, 等. 胃不典型增生和癌组织中Ki67和PTEN蛋白的表达及意义 [J]. 中国普外基础与临床杂志， 2007； 14（3）： 304-307.
10.	Tamura M, Gu J, Takino T, et al. Tumor suppressor PTEN inhibition of cell invasion, migration and growth: differential involvement of focal adhesion kinase and pl30Cas [J]. Cancer Res, 1999； 59(2): 442-449.
11.	Yang L, Kuang LG, Zheng HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma [J]. World J Gastroenterol, 2003； 9(1): 35-39.
12.	Fei G, Ebert MP, Mawrin C, et al. Reduced PTEN expression in gastric cancer and in the gastric mucosa of gastric cancer relatives [J]. Eur J Gastroenterol Hepatol, 2002； 14(3): 297-303.
13.	李海民, 窦科峰, 李韧, 等. 肝癌组织中Fas和FasL mRNA表达水平的变化及其意义 [J]. 中国普外基础与临床杂志， 2005； 12（3）： 284-286.
14.	何贵金, 于发强, 高沁怡, 等. 103钯放射性支架对Fas基因表达影响及与胆管癌细胞凋亡关系研究 [J]. 中国普外基础与临床杂志， 2007； 14（3）： 284-286.
15.	Kusakabe T, Nashimoto A, Honma K, et al. Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach [J]. Histopathology, 2002； 40(1): 71-79.
16.	Morimoto Y, Hizuta A, Ding EX, et al. Funtional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes [J]. Clin Exp immuno1, 1999； 116(1): 84-89.
17.	项良光, 林新龙, 伟青, 等. 耐阿霉素肝癌细胞HepG2表达Fas的变化 [J]. 中国普外基础与临床杂志， 2000； 7（4）： 229-230.
18.	Elnemr A, Ohta T, Yachie A, et al. Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway [J]. Int J Oncol, 2001； 18(2): 311-316.
19.	Nabeshima K, Inoue T, Shimao Y, et al． Front-cells- specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor／scatter factor [J]． Cancer Res, 2000； 60(13): 3364-3369.
20.	Grigioni WF, D’Errico A, Fiorentino M, et al. Gelatinase A (MMP-2) and its mRNA detected in both neoplastic and stromal cells of tumors with different invasive and metastatic properties [J]． Diagn Mol Pathol, 1994； 3(3): 163-169.
21.	Nomura H, Fujimoto N, Seiki M, et al. Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas [J]. Int J Cancer, 1996； 69(1): 9-16.
22.	Ko BK, Cho HR, Choi DW, et al. Reduced expression of tissue inhibitor of metalloproteinase in nodal metastasis of stomach cancer [J]. J Korean Med Sci, 1998； 13 (3)： 286-290.
23.	Otani Y. The collagenase activities, interstitial collagenase and type Ⅳ collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis [J]. Keio J Med, 1990； 39(3): l59-167.
24.	Ko K, Yazumi S, Yoshikawa K, et al. Activation of fibroblast-derived matrix metalloproteinase-2 by colon-cancer cells in non-contact Co-cultures [J]. Int J Cancer, 2000； 87(2): 165-171.
25.	刘伟, 安杰, 张超. 尼美舒利对结肠腺癌细胞MMP-2表达的影响 [J]. 中国普外基础与临床杂志， 2005； 12（6）： 585-588.

1. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [J]. Science, 1997； 275(5308): 1943-1947.
2. Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta [J]. Cancer Res, 1997； 57 (11): 2124-2129.
3. Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumor suppressor gene MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers [J]. Nat Genet, 1997； 15(4): 356-362.
4. 熊敏, 吴一龙主编. 现代肺癌病理与临床 [M]. 北京：北京科学出版社，2003: 97-98.
5. Zhao MD, Hu XM, Sun DJ, et al. Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma [J]. World J Gastroenterol, 2005； 11 (21): 3217-3221.
6. Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas [J]. Br J Cancer, 1999； 79 (11-12): 1828-1835.
7. Yoo CH, Noh SH, Kim YI, et al. Comparison of prognostic significance of nodal staging between old (4th edition) and new (5th edition) UICC TNM classification for gastric carcinoma. International Union Against Cancer [J]. World J Surg, 1999; 23(5): 492-497.
8. Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival [J]. Gastroenterology， 1997; 112(1): 46-54.
9. 陈昊, 李玉民, 何明彦, 等. 胃不典型增生和癌组织中Ki67和PTEN蛋白的表达及意义 [J]. 中国普外基础与临床杂志， 2007； 14（3）： 304-307.
10. Tamura M, Gu J, Takino T, et al. Tumor suppressor PTEN inhibition of cell invasion, migration and growth: differential involvement of focal adhesion kinase and pl30Cas [J]. Cancer Res, 1999； 59(2): 442-449.
11. Yang L, Kuang LG, Zheng HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma [J]. World J Gastroenterol, 2003； 9(1): 35-39.
12. Fei G, Ebert MP, Mawrin C, et al. Reduced PTEN expression in gastric cancer and in the gastric mucosa of gastric cancer relatives [J]. Eur J Gastroenterol Hepatol, 2002； 14(3): 297-303.
13. 李海民, 窦科峰, 李韧, 等. 肝癌组织中Fas和FasL mRNA表达水平的变化及其意义 [J]. 中国普外基础与临床杂志， 2005； 12（3）： 284-286.
14. 何贵金, 于发强, 高沁怡, 等. 103钯放射性支架对Fas基因表达影响及与胆管癌细胞凋亡关系研究 [J]. 中国普外基础与临床杂志， 2007； 14（3）： 284-286.
15. Kusakabe T, Nashimoto A, Honma K, et al. Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach [J]. Histopathology, 2002； 40(1): 71-79.
16. Morimoto Y, Hizuta A, Ding EX, et al. Funtional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes [J]. Clin Exp immuno1, 1999； 116(1): 84-89.
17. 项良光, 林新龙, 伟青, 等. 耐阿霉素肝癌细胞HepG2表达Fas的变化 [J]. 中国普外基础与临床杂志， 2000； 7（4）： 229-230.
18. Elnemr A, Ohta T, Yachie A, et al. Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway [J]. Int J Oncol, 2001； 18(2): 311-316.
19. Nabeshima K, Inoue T, Shimao Y, et al． Front-cells- specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor／scatter factor [J]． Cancer Res, 2000； 60(13): 3364-3369.
20. Grigioni WF, D’Errico A, Fiorentino M, et al. Gelatinase A (MMP-2) and its mRNA detected in both neoplastic and stromal cells of tumors with different invasive and metastatic properties [J]． Diagn Mol Pathol, 1994； 3(3): 163-169.
21. Nomura H, Fujimoto N, Seiki M, et al. Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas [J]. Int J Cancer, 1996； 69(1): 9-16.
22. Ko BK, Cho HR, Choi DW, et al. Reduced expression of tissue inhibitor of metalloproteinase in nodal metastasis of stomach cancer [J]. J Korean Med Sci, 1998； 13 (3)： 286-290.
23. Otani Y. The collagenase activities, interstitial collagenase and type Ⅳ collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis [J]. Keio J Med, 1990； 39(3): l59-167.
24. Ko K, Yazumi S, Yoshikawa K, et al. Activation of fibroblast-derived matrix metalloproteinase-2 by colon-cancer cells in non-contact Co-cultures [J]. Int J Cancer, 2000； 87(2): 165-171.
25. 刘伟, 安杰, 张超. 尼美舒利对结肠腺癌细胞MMP-2表达的影响 [J]. 中国普外基础与临床杂志， 2005； 12（6）： 585-588.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Clinical Significance of PTEN, Fas/FasL and MMP-2 in Gastric Cancer

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