Yu Q, Geng Y, Sicinski P
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 2001 Jun 28;411(6841):1017-21. doi: 10.1038/35082500.
Breast cancer is the most common malignancy among women. Most of these cancers overexpress cyclin D1, a component of the core cell-cycle machinery. We previously generated mice lacking cyclin D1 using gene targeting. Here we report that these cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. However, animals lacking cyclin D1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or Wnt-1. Our analyses revealed that, in mammary epithelial cells, the Neu-Ras pathway is connected to the cell-cycle machinery by cyclin D1, explaining the absolute dependency on cyclin D1 for malignant transformation in this tissue. Our results suggest that an anti-cyclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways.
乳腺癌是女性中最常见的恶性肿瘤。这些癌症中的大多数都过度表达细胞周期蛋白D1，它是核心细胞周期机制的一个组成部分。我们之前利用基因靶向技术培育出了缺乏细胞周期蛋白D1的小鼠。在此我们报告，这些缺乏细胞周期蛋白D1的小鼠对由neu和ras癌基因诱导的乳腺癌具有抗性。然而，缺乏细胞周期蛋白D1的动物对乳腺上皮的其他致癌途径仍完全敏感，比如由c-myc或Wnt-1驱动的途径。我们的分析表明，在乳腺上皮细胞中，Neu-Ras途径通过细胞周期蛋白D1与细胞周期机制相连，这解释了该组织中恶性转化对细胞周期蛋白D1的绝对依赖性。我们的结果表明，抗细胞周期蛋白D1疗法在治疗具有激活的Neu-Ras途径的人类乳腺癌方面可能具有高度特异性。
