利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1對血管生成的影響_《中國普外基礎與臨床雜志》

作者：

任玉萍 , 葉子榮 , 唐泓波 , 張軍 , 張珊 , 陳國慶 , 吳毅平

華中科技大學同濟醫學院附屬同濟醫院整形外科（武漢 430030）;

關鍵詞：

胰島素樣生長因子-1基因敲除鼠血管內皮生長因子乳腺癌人參皂甙基因芯片

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目的探討在低血清胰島素樣生長因子-1（IGF-1）水平與正常IGF-1水平的小鼠乳腺癌模型中應用血管生長抑制劑人參皂甙（GS）Rg3后，IGF-1對血管生成的影響。方法應用7，12-二甲基苯蒽（DMBA）誘導肝臟特異性IGF-1基因敲除鼠（LID鼠）及對照鼠建立原發乳腺癌模型，應用GS Rg3進行干預治療，利用免疫組化法檢測乳腺癌組織中血管內皮生長因子（VEGF）和Ⅷ因子相關抗原（F8-RAg）表達水平，同時利用基因芯片技術檢測小鼠乳腺癌及正常乳腺組織中相關基因的表達情況。結果 LID鼠乳腺癌的發生率低于對照鼠(P＜0.05)； LID鼠乳腺癌組織中VEGF表達水平與微血管密度均低于對照組(P＜0.05)。LID鼠乳腺癌組織中IGF-1、成纖維細胞生長因子(FGF)-1、肝細胞生長因子(HGF)和轉化生長因子(TGF)-β1基因較對照組上調，成纖維細胞生長因子受體(FGFR)-2、血小板源性生長因子(PDGF)-A和PDGF-B基因較對照組下調；應用GS Rg3后，LID鼠乳腺癌組織中VEGFa、表皮生長因子(EGF)、表皮生長因子受體(EGFR)、PDGF-A和FGFR-2基因較對照組上調，而IGF-1和TGF-β1基因較對照組下調。結論 IGF-1促進小鼠乳腺癌的發生、發展，且與血管生長密切相關。血管生長抑制劑可能通過IGF-1及TGF-β1發揮抗腫瘤作用。

引用本文： 任玉萍,葉子榮,唐泓波,張軍,張珊,陳國慶,吳毅平. 利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1對血管生成的影響. 中國普外基礎與臨床雜志, 2008, 15(11): 820-824. doi: 復制

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2. Yakar S, Liu JL, Fernandez AM， et al. Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity [J]. Diabetes, 2001; 50(5)∶ 1110.
3. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma [J]. J Natl Cancer Inst, 1992; 84(24)∶ 1875.
4. Affymetrix, Inc. GeneChip Expression Analysis Technical Manual. http://www.affymetrix.com/support/technical/manual/expression_manual. affx, 2002.
5. Ibrahim YH, Yee D. Insulin-like growth factor-Ⅰ and breast cancer therapy [J]. Clin Cancer Res, 2005; 11(2 Pt 2)∶ 944s.
6. Wu Y, Cui K, Miyoshi K, et al. Reduced circulating insulin-like growth factor Ⅰ levels delay the onset of chemically and genetically induced mammary tumors [J]. Cancer Res, 2003; 63(15)∶4384.
7. Yakar S, Pennisi P, Zhao H, et al. Circulating IGF-1 and its role in cancer: lessons from the IGF-1 gene deletion (LID) mouse [J]. Novartis Found Symp, 2004; 262∶ 3.
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9. van der Meer W, Mackenzie MA, Dinnissen JW, et al. Pseudoplatelets: a retrospective study of their incidence and interference with platelet counting [J]. J Clin Pathol, 2003; 56(10)∶772.
10. Grulich-Henn J, Ritter J, Mesewinkel S, et al. Transport of insulin-like growth factor-Ⅰ across endothelial cell monolayers and its binding to the subendothelial matrix [J]. Exp Clin Endocrinol Diabetes, 2002; 110(2)∶67.
11. Slomiany MG, Rosenzweig SA. Hypoxia-inducible factor-1-dependent and -independent regulation of insulin-like growth factor-1-stimulated vascular endothelial growth factor secretion [J]. J Pharmacol Exp Ther, 2006; 318(2)∶ 666.
12. Lee OH, Bae SK, Bae MH, et al. Identification of angiogenic properties of insulin-like growth factor Ⅱ in in vitro angiogenesis models [J]. Br J Cancer, 2000; 82(2)∶ 385.
13. Jain RK, Duda DG, Clark JW, et al. Lessons from phase Ⅲ clinical trials on anti-VEGF therapy for cancer [J]. Nat Clin Pract Oncol, 2006; 3(1)∶ 24.
14. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine [J]. Genes Dev, 2008; 22(10)∶ 1276.
15. Uutela M, Laurén J, Bergsten E, et al. Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFC genes [J]. Circulation, 2001; 103(18)∶2242.
16. Del Rizzo DF, Yurkova N, Moon MC, et al. Platelet-derived growth factor-induced expression of c-fos in human vascular smooth muscle cells: implications for long-term graft patency [J]. Ann Thorac Surg, 2002; 74(1)∶ 90.
17. van Adrichem LN, Hoogeboom AJ, Wolvius EB. Genetics of craniofacial development [J]. Ned Tijdschr Tandheelkd, 2008; 115(2)∶ 61.
18. Bommireddy R, Doetschman T. TGFbeta1 and Treg cells: alliance for tolerance [J]. Trends Mol Med, 2007; 13(11)∶ 492.
19. Govinden R, Bhoola KD. Genealogy, expression, and cellular function of transforming growth factor-beta [J]. Pharmacol Ther, 2003; 98(2)∶ 257.

《中國普外基礎與臨床雜志》

利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1對血管生成的影響

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《中國普外基礎與臨床雜志》

利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1對血管生成的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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