肝特异性胰岛素样生长因子-Ⅰ基因敲除鼠乳腺癌组织中基因变化及胰岛素样生长因子-Ⅰ对血管生成的影响

目的 探讨低血清胰岛素样生长因子-Ⅰ(IGF-Ⅰ)水平小鼠及正常水平小鼠乳腺癌模型中生长因子相关基因的变化及血管内皮细胞生长因子在乳腺癌组织中的表达与微血管密度的关系.方法 应用DMBA诱导肝脏特异性IGF-Ⅰ基因敲除鼠(LID鼠)及基因未敲除鼠(对照鼠)建立原发乳腺癌模型,基因芯片技术检测小鼠乳腺肿瘤及正常乳腺组织中相关基因的差异表达,免疫组织化学法检测其中VEGF表达及微血管密度.结果 LID鼠组肿瘤的发生时间、生长速度及大小均低于对照组(P＜0.05);(2)LID鼠组肿瘤组织的VEGF表达及MVD均弱于对照鼠组(P＜0.05);(3)LID鼠组肿瘤组织中基因IGF-Ⅰ、IGFBP-4、IGFBP-7较对照组上调,而基因IGF-Ⅱ,IGF-IIR、IGFBP-2、IGFBP-3、IGFBP-5下调.结论 IGF-Ⅰ促进小鼠乳腺癌的发生发展,且与血管生长密切相关.IGF-Ⅰ在肿瘤的发生、发展及转移中可能起重要作用.

The change of gene and the influence to angiogenesis of IGF-Ⅰin liver-specific IGF-Ⅰnook-out mice breast carcinoma tissue

Objective The aim of this study was to determine the variance of growth factor genes in breast carcinoma of mouse model of low and normal serum levels of IGF-Ⅰ,and VEGF expression relationship with MVD in tumor tissues.Methods Establishing the breast carcinoma models with liver-specific IGF-Ⅰ-deficiant (LID) mice in which serum IGF-Ⅰ levels are 25% of that in control mice and control mice by feeding DMBA,using immunohistochemical analysis to detect the VEGF expression and.MVD of tumor tissues.Results ( 1 ) The growth time,growth rate and the size of tumor in LID mice groups is lower than control groups ( P＜0.05 ).( 2 ) The VEGF expression and MVD of LID mice is less than control mice ( P＜0.05 ).( 3 ) Compared to the control,gene IGF-Ⅰ,IGFBP-4 and IGFBP-7 are increased,while gene IGF-Ⅱ ,IGF-IIR,IGFBP-2,IGFBP-3 and IGFBP-5 are decreased in LID mice.Conclusion IGF-Ⅰ may be involved in mouse breast cancer progression and be associated with the growth of vessels.IGF-Ⅰ may play an important role in cancer and metastasis.