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Proc Natl Acad Sci U S A ; 102(31): 11005-10, 2005 Aug 02.
Article in English | MEDLINE | ID: mdl-16043716

ABSTRACT

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.


Subject(s)
Breast Neoplasms/genetics , DNA-Binding Proteins/genetics , Langer-Giedion Syndrome/genetics , Neoplasm Proteins/genetics , Amino Acid Sequence , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , DNA, Neoplasm/genetics , DNA-Binding Proteins/metabolism , Epitopes/genetics , Epitopes/metabolism , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Mice , Mice, Transgenic , Molecular Sequence Data , Neoplasm Proteins/metabolism , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Repressor Proteins , T-Lymphocytes/immunology , Transcription Factors
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