Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin.
Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin.
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发表时间：
1999-10
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通讯作者：
E. DiCarlo;M. Diodoro;K. Boggio;Andrea Modesti;M. Modesti;P. Nanni;G. Forni;P. Musiani
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作者：
E. DiCarlo;M. Diodoro;K. Boggio;Andrea Modesti;M. Modesti;P. Nanni;G. Forni;P. Musiani
对携带激活的大鼠 HER-2/neu 癌基因 (BALB-NeuT) 的 BALB/c (H-2d) 小鼠和携带野生型原癌基因 (FVB-NeuN) 的 FVB (H-2q) 小鼠中产生的乳腺肿瘤进行形态学检查，表明这两种情况都会导致非常像人类的肺泡型小叶癌，其组织型是优先表达的结果小叶导管和小叶上皮中的 HER-2/neu 产物。对肿瘤进展的详细分析表明，通过抗增殖细胞核抗原免疫染色评估，从小叶增生到明显癌的转变与高上皮增殖率相关，并且与通过微血管计数（抗CD31）、抗β3整合素和抗层粘连蛋白免疫染色评估的肿瘤血管生成过程的激活和最大延伸相一致。新血管形成伴随着增生上皮细胞产生血管内皮细胞生长因子和碱性成纤维细胞生长因子。与 BALB-NeuT 肿瘤相比，FVB-NeuN 小鼠中产生的肿瘤几乎不存在 E-钙粘蛋白表达，这可能解释了它们的高转移潜力。然而，尽管它们的动力学不同，但在两种菌株中观察到的肺转移在组织学上相似并且类似于原发肿瘤。因此，这两种菌株都可以作为模型用于“体内”研究肺泡型小叶乳腺癌的起源和进展以及测试新的治疗方法。
Morphologic examinations of mammary neoplasias arising in BALB/c (H-2d) mice carrying the activated rat HER-2/neu oncogene (BALB-NeuT), and in FVB (H-2q) mice bearing the wild-type proto-oncogene (FVB-NeuN), indicate that both conditions result in a very human-like lobular carcinoma of alveolar type, whose histotype is the result of the preferential expression of HER-2/neu products in the epithelium of lobular ducts and lobules. Detailed analysis of tumor progression indicates that transition from lobular hyperplasia to overt carcinoma is associated with a high epithelial proliferation rate, as assessed by anti-proliferating cell nuclear antigen immunostaining, and coincides with the activation and maximal extension of tumor angiogenic process as assessed by microvessel count (anti-CD31), anti-beta3 integrin, and anti-laminin immunostaining. Neovascularization is accompanied by vascular endothelial cell growth factor and basic fibroblast growth factor production by hyperplastic epithelial cells. By contrast with the BALB-NeuT tumors, E-cadherin expression is almost nonexistent in those arising in FVB-NeuN mice and this may explain their high metastatic potential. Despite their different kinetics, however, the lung metastases observed in both strains are histologically similar and resemble the primary tumor. Both strains can thus be proposed as models for "in vivo" investigation of the origin and progression of the alveolar type of lobular mammary carcinoma and the testing of new therapeutic approaches.