Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial–mesenchymal transition
- 2 July 2007
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 26 (57), 7859-7871
- https://doi.org/10.1038/sj.onc.1210593
Abstract
Metaplastic carcinoma of the breast (MCB) is a poorly understood subtype of breast cancer. It is generally characterized by the coexistence of ductal carcinomatous and transdifferentiated sarcomatous components, but the underlying molecular alterations, possibly related to epithelial-mesenchymal transition (EMT), remain elusive. We performed transcriptional profiling using half-a-genome oligonucleotide microarrays to elucidate genetic profiles of MCBs and their differences to those of ductal carcinoma of breasts (DCBs) using discarded specimens of four MCBs and 34 DCBs. Unsupervised clustering disclosed distinctive expression profiles between MCBs and DCBs. Supervised analysis identified gene signatures discriminating MCBs from DCBs and between MCB subclasses. Notably, many of the discriminator genes were associated with downregulation of epithelial phenotypes and with synthesis, remodeling and adhesion of extracellular matrix, with some of them have known or inferred roles related to EMT. Importantly, several of the discriminator genes were upregulated in a mutant Snail-transfected MCF7 cell known to exhibit features of EMT, thereby indicating a crucial role for EMT in the pathogenesis of MCBs. Finally, the identification of SPARC and vimentin as poor prognostic factors reinforced the role of EMT in cancer progression. These data advance our understanding of MCB and offer clues to the molecular alterations underlying EMT.This publication has 33 references indexed in Scilit:
- Spindle Cell (Sarcomatoid) Carcinoma of the BreastThe American Journal of Surgical Pathology, 2006
- An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgenOncogene, 2006
- Metaplastic carcinoma of the breast Clinical presentation, treatment results and prognostic factorsActa Oncologica, 2006
- Reactivation of Hox gene expression during bone regenerationJournal of Orthopaedic Research, 2005
- Metaplastic breast carcinoma: clinical–pathologic characteristics and HER2/neu expressionBreast Cancer Research and Treatment, 2005
- SPARC and tumor growth: Where the seed meets the soil?Journal of Cellular Biochemistry, 2004
- CCAAT/enhancer binding protein beta (C/EBPβ)-2 transforms normal mammary epithelial cells and induces epithelial to mesenchymal transition in cultureOncogene, 2003
- Epiplakin, a Novel Member of the Plakin Family Originally Identified as a 450-kDa Human Epidermal AutoantigenOnline Journal of Public Health Informatics, 2001
- Gene Ontology: tool for the unification of biologyNature Genetics, 2000
- Loss of expression of the candidate tumor suppressor gene ZAC in breast cancer cell lines and primary tumorsOncogene, 1999