Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases
Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases
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DOI：
10.1016/s0002-9440(10)63568-7
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发表时间：
2003-11-01
影响因子：
6
通讯作者：
Pollard, JW
中科院分区：
文献类型：
--
作者：
Lin, EY;Jones, JG;Pollard, JW
动物模型是分析人类乳腺癌诱发机制的有力工具。在这里，我们报告了一种由乳腺上皮中多瘤中 T 癌蛋白 (PyMT) 表达引起的乳腺癌小鼠模型中乳腺肿瘤进展的详细分析，及其与人类乳腺肿瘤的比较。在 PyMT 小鼠中，从癌前阶段到恶性阶段的四个明显可识别的肿瘤进展阶段发生在单个原发肿瘤灶中，并且这种恶性转变之后是高频率的远处转移。这些阶段与分类为良性或原位增殖性病变至浸润性癌的人类乳腺疾病相当。除了与人类乳腺癌的形态学相似之外，PyMT 诱导的肿瘤中生物标志物的表达也与人类不良预后相关的生物标志物表达一致。这些包括雌激素和孕激素受体的丧失以及整合素-β1 表达的丧失，以及 PyMT 诱导的肿瘤在进展到恶性阶段时 ErbB2/Neu 和 cycbnD1 的持续表达。白细胞浸润增加也与恶性转变密切相关。这项研究表明，PyMT 小鼠模型是了解人类肿瘤进展生物学的绝佳模型。
Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer caused by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison to human breast tumors. In PyMT mice, four distinctly identifiable stages of tumor progression from premalignant to malignant stages occur in a single primary tumor focus and this malignant transition is followed by a high frequency of distant metastasis. These stages are comparable to human breast diseases classified as benign or in situ proliferative lesions to invasive carcinomas. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors as well as integrin-beta1 expression and the persistent expression of ErbB2/Neu and cycbnD1 in PyMT-induced tumors as they progress to the malignant stage. An increased leukocytic infiltration was also closely associated with the malignant transition. This study demonstrates that the PyMT mouse model is an excellent one to understand the biology of tumor progression in humans.