1. The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer
- Author
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Jean M. Shortreed, Devender Singh-Sandhu, Melinda Donovan, Corey Lovitt, Artur Pedyczak, Wedad Hanna, Jane E. Armes, Scott Gallichan, Ray Oomen, Gustavo V. Mallo, Mark Parrington, Judith Zubovits, Kevin E Kwok, Jalil Hakimi, Kurt C. Gish, Pamela Dunn, James Tartaglia, Laszlo Radvanyi, Neil L. Berinstein, and Deon J. Venter
- Subjects
Langer-Giedion Syndrome ,Microarray ,T-Lymphocytes ,T cell ,Molecular Sequence Data ,Breast Neoplasms ,Mice, Transgenic ,In situ hybridization ,Biology ,Epitopes ,Mice ,Breast cancer ,Antigens, Neoplasm ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Amino Acid Sequence ,RNA, Messenger ,RNA, Neoplasm ,Gene ,Oligonucleotide Array Sequence Analysis ,Multidisciplinary ,Gene Expression Profiling ,DNA, Neoplasm ,Biological Sciences ,Ductal carcinoma ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Neoplasm Proteins ,DNA-Binding Proteins ,Repressor Proteins ,Gene expression profiling ,medicine.anatomical_structure ,Cancer research ,Female ,Transcription Factors - 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, includingin situhybridization, 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 carcinomain situand 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.
- Published
- 2005
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