Huang Shixia, Li Yi, Chen Yidong, Podsypanina Katrina, Chamorro Mario, Olshen Adam B, Desai Kartiki V, Tann Anne, Petersen David, Green Jeffrey E, Varmus Harold E
Program in Cancer Biology and Genetics, Sloan-Kettering Institute, New York, NY 10021, USA.
Genome Biol. 2005;6(10):R84. doi: 10.1186/gb-2005-6-10-r84. Epub 2005 Sep 30.
In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development.
We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV-Wnt-1 transgenic mice, and 12 mammary tumors from MMTV-Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes.
We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression.
在人类乳腺癌中，正常乳腺细胞通常会发展为增生、原位导管癌、浸润性癌和转移。与这种逐步进展相关的基因表达变化尚不清楚。携带小鼠乳腺肿瘤病毒（MMTV）-Wnt-1的转基因小鼠表现出乳腺肿瘤发生的离散步骤，包括增生、浸润性导管癌和远处转移。因此，这些小鼠可能是发现癌症发展过程中基因表达变化的有用模型。
我们使用cDNA微阵列来确定来自MMTV-Wnt-1转基因小鼠的五个正常乳腺、七个增生性乳腺和23个乳腺肿瘤以及来自MMTV-Neu转基因小鼠的12个乳腺肿瘤的表达谱。使用脂肪组织来控制乳腺附近的脂肪细胞。在这些分析中，我们发现正常处女乳腺向增生组织和乳腺肿瘤的进展在每个步骤中都伴随着数百个基因表达的差异。其中一些差异似乎是Wnt信号传导效应所特有的；其他差异似乎是由Neu和Wnt-1癌基因诱导的肿瘤所共有的。
我们描述了与小鼠乳腺癌发展相关的基因表达模式，并鉴定了可能是致癌事件重要靶点的基因。所产生的表达数据为阐明乳腺癌发展所涉及的分子机制提供了资源，特别是通过鉴定在癌症起始和进展中至关重要的基因。
