Article
Identification of clinically relevant genes in a functional model of chromosome 8 mediated breast tumor suppression
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Published: | March 20, 2006 |
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Several lines of evidence suggest that chromosome 8 harbors one or more tumor suppressor genes in breast cancer. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression profiling using GeneChip DNA microarray analysis identified a set of 109 altered genes (CT8-ps) associated with these phenotypic alterations. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Expression analysis of CT8-ps in a series of human breast tumors revealed several associations with clinicopathological features, including tumor size, grading and age at diagnosis. The combined approach of microcell-mediated chromosome transfer and expression difference analysis provides a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer. The detailed contextual characterization of the identified CT8-ps will determine the extent of their involvement in breast tumorigenesis.