ADAM9在乳腺癌中的表達及意義_《中國普外基礎與臨床雜志》

作者：

錢宏美 ^1,2 , 李俊生 ¹ , 張亞男 ¹ , 魏曉瑩 ³ , 嵇振嶺 ¹

1.東南大學附屬中大醫院普外科(南京210009）;;
2.安徽省馬鞍山市人民醫院普外科(馬鞍山 243000);;
3.東南大學附屬中大醫院病理科(南京210009）;

關鍵詞：

乳腺癌去整合素金屬蛋白酶9 逆轉錄多聚酶鏈聚合反應免疫組織化學

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的探討去整合素金屬蛋白酶9(ADAM9)在乳腺癌中的表達及意義。
方法采用逆轉錄多聚酶鏈聚合反應（RT-PCR）法和免疫組織化學方法檢測乳腺癌組織、距離癌旁≥5 cm的正常乳腺組織及腋窩淋巴結組織中ADAM9的表達，并分析ADAM9表達與乳腺癌臨床病理特征之間的關系。
結果 ADAM9 mRNA在乳腺癌組織中的表達較正常乳腺組織(未檢測到ADAM9 mRNA的表達)明顯增強。ADAM9蛋白表達陽性率在乳腺癌組織中明顯高于正常乳腺組織(P lt;0.05)，其在乳腺癌轉移淋巴結中的表達明顯高于非轉移淋巴結及相應原發灶中的表達(P lt;0.05)。乳腺癌組織中ADAM9蛋白表達陽性率與其淋巴結轉移和組織學分級有關(P lt;0.05)。
結論 ADAM9在乳腺癌中表達上調，可能參與了乳腺癌發生、發展過程。

引用本文： 錢宏美,李俊生,張亞男,魏曉瑩,嵇振嶺. ADAM9在乳腺癌中的表達及意義. 中國普外基礎與臨床雜志, 2010, 17(9): 927-931. doi: 復制

1.	Jemal A, Siegel R, Ward E, et al. Cancer satistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 225249.
2.	上海市疾病預防控制中心. 2006年上海市市區惡性腫瘤發病率 [J]. 腫瘤, 2009; 29(9): 918.
3.	Peduto L, Reuter VE, Shaffer DR, et al. Critical function for ADAM9 in mouse prostate cancer [J]. Cancer Res, 2005; 65(20): 93129319.
4.	Grützmann R, Lüttges J, Sipos B, et al. ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma [J]. Br J Cancer, 2004; 90(5): 10531058.
5.	Hirao T, Nanba D, Tanaka M, et al. Overexpression of ADAM9 enhances growth factormediated recycling of Ecadherin in human colon cancer cell line HT29 cells [J]. Exp Cell Res, 2006; 312(3): 331339.
6.	Zigrino P, Mauch C, Fox JW, et al. Adam9 expression and regulation in human skin melanoma and melanoma cell lines [J]. Int J Cancer, 2005; 116(6): 853859.
7.	中國抗癌協會乳腺癌專業委員會. 中國抗癌協會乳腺癌診治指南與規范(2007版) [J]. 中國癌癥雜志, 2007; 17(5): 410429.
8.	Parham DM. Mitotic activity and histological grading of breast cancer [J]. Pathol Annu, 1995; 30(Pt 1): 189207.
9.	施文, 李俊生. 結腸癌組織中ADAM9的表達及其與微血管密度的關系 [J]. 東南大學學報（醫學版）， 2009; 28(4): 274277.
10.	Schwettmann L, Tschesche H. Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin [J]. Protein Expr Purif, 2001; 21(1): 6570.
11.	Nath D, Slocombe PM, Webster A, et al. Meltrin γ (ADAM9) mediates cellular adhesion through α6β1 integrin, leading to a marked induction of fibroblast cell motility [J]. J Cell Sci, 2000; 113(Pt 12): 23192328.
12.	Karadag A, Zhou M, Croucher PI. ADAM9 (MDC9/meltrinγ), a member of the a disintegrin and metalloproteinase family, regulates myelomacellinduced interleukin6 production in osteoblasts by direct interaction with the αⅤβ5 integrin [J]. Blood, 2006; 107(8): 32713278.
13.	Zigrino P, Steiger J, Fox JW, et al. Role of ADAM9 disintegrincysteinerich domains in human keratinocyte migration [J]. J Biol Chem, 2007; 282(42): 3078530793.
14.	Mazzocca A, Coppari R, De Franco R, et al. A secreted form of ADAM9 promotes carcinoma invasion through tumorstromal interactions [J]. Cancer Res, 2005; 65(11): 47284738.
15.	Shintani Y, Higashiyama S, Ohta M, et al. Overexpression of ADAM9 in nonsmall cell lung cancer correlates with brain metastasis [J]. Cancer Res, 2004; 64(12): 41904196.
16.	Sung SY, Kubo H, Shigemura K, et al. Oxidative stress induces ADAM9 protein expression in human prostate cancer cells [J]. Cancer Res, 2006; 66(19): 95199526.
17.	Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J]. Cancer Cell, 2006; 10(6): 529541.
18.	CarlMcGrath S, Lendeckel U, Ebert M, et al.The disintegrinmetalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer [J]. Int J Oncol, 2005; 26(1): 1724.
19.	Johnstone P, Sung S, Anderson C, et al. The natural product honokiol potentiates radiation sensitization induced by SiRNA ADAM9 knockdown in prostate cancer cells [J]. Radiother Oncol, 2006; 78: S76S77.
20.	Weskamp G, Cai H, Brodie TA, et al. Mice lacking the metalloproteasedisintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life [J]. Mol Cell Biol, 2002; 22(5): 15371544.
21.	O’Shea C, McKie N, Buggy Y, et al. Expression of ADAM9 mRNA and protein in human breast cancer [J]. Int J Cancer, 2003； 105(6): 754761.
22.	Park D, Kresen R, Noren T, et al. Ki67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications[J]. Virchows Arch, 2007; 451(1): 1118.
23.	Shim H, Lau SK, Devi S, et al. Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by liganddependent degradation and HIF1α [J]. Biochem Biophys Res Commun, 2006; 346(1): 252258.
24.	Goedheer AJ, Portengen H, Klijn JG, et al. How ADAM9 and ADAM11 differentially from estrogen receptor predict response to tamoxifen treatment in patients with recurrent breast cancer: a retrospective study [J]. Clin Cancer Res, 2005； 11(20): 73117321.
25.	Fritzsche FR, Wassermann K, Jung M, et al. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression [J]. BMC Cancer, 2008； 8: 179187.

1. Jemal A, Siegel R, Ward E, et al. Cancer satistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 225249.
2. 上海市疾病預防控制中心. 2006年上海市市區惡性腫瘤發病率 [J]. 腫瘤, 2009; 29(9): 918.
3. Peduto L, Reuter VE, Shaffer DR, et al. Critical function for ADAM9 in mouse prostate cancer [J]. Cancer Res, 2005; 65(20): 93129319.
4. Grützmann R, Lüttges J, Sipos B, et al. ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma [J]. Br J Cancer, 2004; 90(5): 10531058.
5. Hirao T, Nanba D, Tanaka M, et al. Overexpression of ADAM9 enhances growth factormediated recycling of Ecadherin in human colon cancer cell line HT29 cells [J]. Exp Cell Res, 2006; 312(3): 331339.
6. Zigrino P, Mauch C, Fox JW, et al. Adam9 expression and regulation in human skin melanoma and melanoma cell lines [J]. Int J Cancer, 2005; 116(6): 853859.
7. 中國抗癌協會乳腺癌專業委員會. 中國抗癌協會乳腺癌診治指南與規范(2007版) [J]. 中國癌癥雜志, 2007; 17(5): 410429.
8. Parham DM. Mitotic activity and histological grading of breast cancer [J]. Pathol Annu, 1995; 30(Pt 1): 189207.
9. 施文, 李俊生. 結腸癌組織中ADAM9的表達及其與微血管密度的關系 [J]. 東南大學學報（醫學版）， 2009; 28(4): 274277.
10. Schwettmann L, Tschesche H. Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin [J]. Protein Expr Purif, 2001; 21(1): 6570.
11. Nath D, Slocombe PM, Webster A, et al. Meltrin γ (ADAM9) mediates cellular adhesion through α6β1 integrin, leading to a marked induction of fibroblast cell motility [J]. J Cell Sci, 2000; 113(Pt 12): 23192328.
12. Karadag A, Zhou M, Croucher PI. ADAM9 (MDC9/meltrinγ), a member of the a disintegrin and metalloproteinase family, regulates myelomacellinduced interleukin6 production in osteoblasts by direct interaction with the αⅤβ5 integrin [J]. Blood, 2006; 107(8): 32713278.
13. Zigrino P, Steiger J, Fox JW, et al. Role of ADAM9 disintegrincysteinerich domains in human keratinocyte migration [J]. J Biol Chem, 2007; 282(42): 3078530793.
14. Mazzocca A, Coppari R, De Franco R, et al. A secreted form of ADAM9 promotes carcinoma invasion through tumorstromal interactions [J]. Cancer Res, 2005; 65(11): 47284738.
15. Shintani Y, Higashiyama S, Ohta M, et al. Overexpression of ADAM9 in nonsmall cell lung cancer correlates with brain metastasis [J]. Cancer Res, 2004; 64(12): 41904196.
16. Sung SY, Kubo H, Shigemura K, et al. Oxidative stress induces ADAM9 protein expression in human prostate cancer cells [J]. Cancer Res, 2006; 66(19): 95199526.
17. Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J]. Cancer Cell, 2006; 10(6): 529541.
18. CarlMcGrath S, Lendeckel U, Ebert M, et al.The disintegrinmetalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer [J]. Int J Oncol, 2005; 26(1): 1724.
19. Johnstone P, Sung S, Anderson C, et al. The natural product honokiol potentiates radiation sensitization induced by SiRNA ADAM9 knockdown in prostate cancer cells [J]. Radiother Oncol, 2006; 78: S76S77.
20. Weskamp G, Cai H, Brodie TA, et al. Mice lacking the metalloproteasedisintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life [J]. Mol Cell Biol, 2002; 22(5): 15371544.
21. O’Shea C, McKie N, Buggy Y, et al. Expression of ADAM9 mRNA and protein in human breast cancer [J]. Int J Cancer, 2003； 105(6): 754761.
22. Park D, Kresen R, Noren T, et al. Ki67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications[J]. Virchows Arch, 2007; 451(1): 1118.
23. Shim H, Lau SK, Devi S, et al. Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by liganddependent degradation and HIF1α [J]. Biochem Biophys Res Commun, 2006; 346(1): 252258.
24. Goedheer AJ, Portengen H, Klijn JG, et al. How ADAM9 and ADAM11 differentially from estrogen receptor predict response to tamoxifen treatment in patients with recurrent breast cancer: a retrospective study [J]. Clin Cancer Res, 2005； 11(20): 73117321.
25. Fritzsche FR, Wassermann K, Jung M, et al. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression [J]. BMC Cancer, 2008； 8: 179187.

《中國普外基礎與臨床雜志》

ADAM9在乳腺癌中的表達及意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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《中國普外基礎與臨床雜志》

ADAM9在乳腺癌中的表達及意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料