Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 31, Pages 11005-11010Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0500904102
Keywords
gene expression profiling; immunohistochemistry
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A comprehensive differential gene expression screen on a panel of 54 breast tumors and > 200 normal tissue samples using DNA microarrays revealed 15 genes specifically overexpressed in breast cancer. One of the most prevalent genes found was trichorhinophalangeal syndrome type 1 (TRPS-1), a gene previously shown to be associated with three rare autosomal dominant genetic disorders known as the trichorhinophalangeal syndromes. A number of corroborating methodologies, including in situ hybridization, e-Northern analysis using ORF EST (ORESTES) and Unigene EST abundance analysis, immunoblot and immunofluorescence analysis of breast tumor cell lines, and immunohistochemistry, confirmed the microarray findings. Immunohistochemistry analysis found TRPS-1 protein expressed in > 90% of early- and late-stage breast cancer, including ductal carcinoma in situ and invasive ductal, lobular, and papillary carcinomas. The TRPS-1 gene is also immunogenic with processed and presented peptides activating T cells found after vaccination of HLA-A2.1 transgenic mouse. Human T cell lines from HLA-A*0201(+) female donors exhibiting TRPS-1-specific cytotoxic T lymphocyte activity could also be generated.
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