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Distinct gene expression signatures during development of distant metastasis
Authors:Jeonghoon Heo  Ju-seog Lee  Sun-Hee Leem
Institution:1. Department of Molecular Biology and Immunology, College of Medicine, Kosin University, 34 Amnam-dong, Seo-gu, Busan, 602-703, Korea
2. Institute of Medical Science, College of Medicine, Kosin University, 34 Amnam-dong, Seo-gu, Busan, 602-703, Korea
3. Department of System Biology, University of Texas, MD Anderson Cancer Center, Houston, TX, 77054, USA
4. Department of Biological Science, College of Natural Science, Dong-A University, 840 Hadan 2-dong, Saha-gu, Busan, 604-714, Korea
Abstract:Using cDNA microarrays, we have conducted a systematic characterization of global gene expression in v-raf or v-raf/v-myc transformed rat liver epithelial (RLE) cell lines exhibiting both non-metastatic and metastatic phenotypes. Seven transformed cell lines were compared with the non-transformed parental RLE cell. The hierarchical clustering analysis of gene expression profiles revealed two groups reflecting the in vivo metastatic potential of the cells. Surprisingly, one non-metastatic cell line T1 was co-clustered with metastatic cell lines, suggesting that T1 underwent significant genetic changes. The T1 cell line was further compared against all the metastatic cell lines in order to reveal the critical genes required for metastatic conversion but not expressed in the T1. These data demonstrated that expression of genes involved in apoptosis and immune cell homing were altered in all metastatic cell lines. Survival of both intravasated cells in circulation systems and extravasated cells in a new tissue environment might be critical for the final step in the metastatic process. Our study provides gene expression signatures consistent with two critical events in the metastatic process, namely, the acquisition of early homing capacity and increased survival potential of the tumor cells.
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