Study of Influence of IGF-1 on Angiogenesis by Using IGF-1 Deficient Mice Breast Cancer Models_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

REN Yuping , YE Zirong , TANG Hongbo , ZHANG Jun , ZHANG Shan , CHEN Guoqing , WU Yiping

Department of Plastic Surgery, The Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;

Corresponding author：

Keywords：

Insulin-like growth factor-1 knock-out mice; Vascular endothelial growth factor; Breast cancer; Ginsenoside; Gene chip

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Objective To determine the effect of insulin-like growth factor-1 (IGF-1) on angiogenesis in mouse breast cancer model of lower and normal serum IGF-1 levels after using angiogenesis inhibitor ginsenoside Rg3 （GS Rg3）. Methods The breast cancer models were established in control mice and liver specific IGF-1 deficient (LID) mice by feeding DMBA and were treated with GS Rg3. Vascular endothelial growth factor (VEGF) and F8-RAg were detected by immunohistochemical method in breast cancer tissues. IGF-1 gene and angiogenesis relating genes were detected by gene chip in breast cancer and normal breast tissue. Results The incidence rate of breast cancer in LID mice was lower than that in control mice (P＜0.05). VEGF expression and microvessel density of LID mice were lower than those in control mice (P＜0.05). Compared to the control mice, IGF-1, FGF-1, TGF-β1 and HGF genes were increased, and FGFR-2, PDGF-A and PDGF-B genes were decreased in breast cancer of LID mice. After GS Rg3 treatment, VEGFa, EGF, EGFR, PDGF-A and FGFR-2 genes were increased, IGF-1 and TGF-β1 genes were decreased in breast cancer of LID mice compared with the control mice. Conclusion IGF-1 may be involved in mouse breast cancer progression and associated with the growth of blood vessels. Angiogenesis inhibitor may play an antitumor role by IGF-1 and TGF-β1.

Citation： REN Yuping,YE Zirong,TANG Hongbo,ZHANG Jun,ZHANG Shan,CHEN Guoqing,WU Yiping. Study of Influence of IGF-1 on Angiogenesis by Using IGF-1 Deficient Mice Breast Cancer Models. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(11): 820-824. doi: Copy

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1. Yakar S, Liu JL, Stannard B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor Ⅰ [J]. Proc Natl Acad Sci USA, 1999; 96(13)∶ 7324.
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.
8. 王喜，凌昌全. 中药有效成份抗肿瘤转移的研究进展 [J]. 中国中西医结合杂志, 2004; 24(2)∶ 178.
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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of Influence of IGF-1 on Angiogenesis by Using IGF-1 Deficient Mice Breast Cancer Models

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