- MeSH
- Neoplasms, Experimental genetics MeSH
- Animals, Genetically Modified MeSH
- Genes, env MeSH
- Genes, src MeSH
- Major Histocompatibility Complex MeSH
- Animals, Inbred Strains MeSH
- Chickens * MeSH
- Animals, Laboratory MeSH
- Neoplasm Metastasis MeSH
- Disease Models, Animal * MeSH
- Oncogenes MeSH
- Sarcoma, Avian * MeSH
- Graft Rejection MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Genes, src * MeSH
- Heterografts MeSH
- Virus Integration MeSH
- Rats MeSH
- Chickens virology MeSH
- Cell Line, Tumor MeSH
- Poultry Diseases history virology MeSH
- Periodicals as Topic history MeSH
- Proviruses genetics physiology MeSH
- Sarcoma, Avian history virology MeSH
- Neoplasm Transplantation MeSH
- Cell Transformation, Viral MeSH
- Rous sarcoma virus genetics isolation & purification physiology MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Rats MeSH
- Animals MeSH
- Publication type
- Autobiography MeSH
- Biography MeSH
- Historical Article MeSH
- Editorial MeSH
- Geographicals
- Czechoslovakia MeSH
- Maryland MeSH
UNLABELLED: Comparing the gene expression profiles of metastatic and nonmetastatic cells has the power to reveal candidate metastasis-associated genes, whose involvement in metastasis can be experimentally tested. In this study, differentially expressed genes were explored in the v-src-transformed metastatic cell line PR9692 and its nonmetastatic subclone PR9692-E9. First, the contribution of homeodomain only protein X (HOPX) in metastasis formation and development was assessed. HOPX-specific knockdown decreased HOPX expression in the nonmetastatic subclone and displayed reduced cell motility in vitro. Critically, HOPX knockdown decreased the in vivo metastatic capacity in a syngeneic animal model system. Genomic analyses identified a cadre of genes affected by HOPX knockdown that intersected significantly with genes previously found to be differentially expressed in metastatic versus nonmetastatic cells. Furthermore, 232 genes were found in both screens with at least a two-fold change in gene expression, and a number of high-confidence targets were validated for differential expression. Importantly, significant changes were demonstrated in the protein expression level of three metastatic-associated genes (NCAM, FOXG1, and ITGA4), and knockdown of one of the identified HOPX-regulated metastatic genes, ITGA4, showed marked inhibition of cell motility and metastasis formation. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns. IMPLICATIONS: This study provides new mechanistic insight into a HOPX-regulated metastatic dissemination signature.
- MeSH
- Cell Cycle MeSH
- Down-Regulation MeSH
- Sarcoma, Experimental genetics pathology secondary MeSH
- Forkhead Transcription Factors genetics metabolism MeSH
- Gene Knockdown Techniques MeSH
- Genes, src MeSH
- Homeodomain Proteins genetics metabolism MeSH
- Chickens MeSH
- Neoplasm Metastasis genetics MeSH
- Neural Cell Adhesion Molecules genetics metabolism MeSH
- Cell Transformation, Neoplastic genetics MeSH
- Cell Line, Tumor MeSH
- Cell Movement MeSH
- Avian Proteins genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Gene Expression Profiling MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This chapter provides a personal insight into the scientific and social atmosphere in former Czechoslovakia. It covers the period of the rise of Hasek's immunologic school and application of immunologic tolerance to Rous sarcoma virus (RSV) heterotransmission. These approaches permitted establishment of a new model of mammalian cells transformed by RSV (virogenic XC cells), where the noninfectious viral genome was kept indefinitely as new genetic information (provirus). RSV was rescued from nonpermissive mammalian cells by fusion (complementation) with permissive chicken fibroblasts; this opened the way to understanding virus nonpermissiveness. Mammalian cells transformed by the reverse transcript of v-src mRNA were characterized, and the resulting provirus was shown to be highly oncogenic for chickens and to carry tumor-specific transplantation antigen. Other areas covering epigenetic reversion of RSV-transformed cells and long-term persistence of chicken leucosis viruses in foreign avian species are discussed.
- MeSH
- History, 20th Century MeSH
- Financing, Organized MeSH
- Genes, src MeSH
- Virus Integration MeSH
- Medical Oncology history MeSH
- Oncogenic Viruses physiology MeSH
- Cell Transformation, Viral MeSH
- Rous sarcoma virus physiology MeSH
- Research MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- Animals MeSH
- Publication type
- Historical Article MeSH
- Geographicals
- Czechoslovakia MeSH
- MeSH
- Genes, src MeSH
- Myocardial Ischemia metabolism pathology MeSH
- Ischemic Preconditioning, Myocardial MeSH
- Mice MeSH
- Myocardial Reperfusion MeSH
- Reperfusion Injury pathology prevention & control MeSH
- Arrhythmias, Cardiac diagnosis MeSH
- Protein-Tyrosine Kinases genetics MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
