ABSTRACT: INTRODUCTION: 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 to cases of male gynecomastia and female breast cancers. METHODS: Paraffin-blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and 5 cases of male gynecomastia, and 10 female ductal breast carcinomas. RNA harvested was hybridized to miRNA microarrays (~1100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicates). 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. RESULTS: We identified a male breast cancer miRNA signature composed by a large portion of under-expressed miRNAs. In particular, 17 miRNAs with increased expression and 26 with decreased expression were identified in male breast cancer compare to gynecomastia. Among these miRNAs some had well characterized cancer development association and some showed a de-regulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male to female breast cancers miRNA expression signatures, 17 significantly deregulated miRNAs were observed (4 over-expressed and 13 under-expressed in male breast cancers). The HOXD10 and VEGF genes immunohistochemical expression significantly follows the corresponding miRNA deregulation. CONCLUSIONS: 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.
MicroRNA expression profiling of male breast cancer.
VOLINIA, Stefano;CROCE, Carlo Maria;
2009
Abstract
ABSTRACT: INTRODUCTION: 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 to cases of male gynecomastia and female breast cancers. METHODS: Paraffin-blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and 5 cases of male gynecomastia, and 10 female ductal breast carcinomas. RNA harvested was hybridized to miRNA microarrays (~1100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicates). 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. RESULTS: We identified a male breast cancer miRNA signature composed by a large portion of under-expressed miRNAs. In particular, 17 miRNAs with increased expression and 26 with decreased expression were identified in male breast cancer compare to gynecomastia. Among these miRNAs some had well characterized cancer development association and some showed a de-regulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male to female breast cancers miRNA expression signatures, 17 significantly deregulated miRNAs were observed (4 over-expressed and 13 under-expressed in male breast cancers). The HOXD10 and VEGF genes immunohistochemical expression significantly follows the corresponding miRNA deregulation. CONCLUSIONS: 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
