Department of Urology, Thomas Jefferson University - Kimmel Cancer Center, 1112 College Building, 1025 Walnut Street, PA 19107, USA.
Breast Cancer Res. 2009;11(4):R58. doi: 10.1186/bcr2348. Epub 2009 Aug 10.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers.
Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and five cases of male gynecomastia, and from 10 female ductal breast carcinomas. The RNA harvested was hybridized to miRNA microarrays (~1,100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicate). To further support the microarray data, an immunohistochemical analysis for two specific miRNA gene targets (HOXD10 and VEGF) was performed in a small series of male breast carcinoma and gynecomastia samples.
We identified a male breast cancer miRNA signature composed of a large portion of underexpressed miRNAs. In particular, 17 miRNAs with increased expression and 26 miRNAs with decreased expression were identified in male breast cancer compared with gynecomastia. Among these miRNAs, some had well-characterized cancer development association and some showed a deregulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male with female breast cancer miRNA expression signatures, 17 significantly deregulated miRNAs were observed (four overexpressed and 13 underexpressed in male breast cancers). The HOXD10 and VEGF gene immunohistochemical expression significantly follows the corresponding miRNA deregulation.
Our results suggest that specific miRNAs may be directly involved in male breast cancer development and that they may represent a novel diagnostic tool in the characterization of specific cancer gene targets.
MicroRNAs（miRNAs）是一类小的非编码 RNA，通过靶向 mRNAs 并触发翻译抑制或 RNA 降解来控制基因表达。它们的异常表达可能与人类疾病有关，包括癌症。为了验证存在一种特定的 miRNA 表达特征可以描述男性乳腺癌的假说，我们对一系列男性乳腺癌进行了 miRNA 微阵列分析，并将其与男性乳腺增生症和女性乳腺癌病例进行了比较。
在托马斯杰斐逊大学病理学系从 28 名男性患者中获得石蜡块，包括 23 例乳腺癌和 5 例男性乳腺增生症，以及 10 例女性乳腺导管癌。收获的 RNA 与 miRNA 微阵列杂交（~1100 个 miRNA 探针，包括 326 个人类和 249 个小鼠 miRNA 基因，重复点样）。为了进一步支持微阵列数据，对一小部分男性乳腺癌和乳腺增生症样本进行了两个特定 miRNA 基因靶标（HOXD10 和 VEGF）的免疫组织化学分析。
我们确定了一个由大量低表达 miRNA 组成的男性乳腺癌 miRNA 特征。与乳腺增生症相比，男性乳腺癌中发现了 17 个 miRNA 表达增加，26 个 miRNA 表达降低。在这些 miRNA 中，一些与癌症发展有很好的相关性，一些在癌症标本中表现出与之前在女性乳腺癌发表的特征中观察到的类似的失调。比较男性与女性乳腺癌 miRNA 表达特征，观察到 17 个显著失调的 miRNA（男性乳腺癌中四个上调，13 个下调）。HOXD10 和 VEGF 基因的免疫组织化学表达明显遵循相应的 miRNA 失调。
我们的结果表明，特定的 miRNA 可能直接参与男性乳腺癌的发展，并且它们可能代表一种用于鉴定特定癌症基因靶标的新的诊断工具。
