Chromosomal changes in high- and low-invasive mouse lung adenocarcinoma cell strains derived from early passage mouse lung adenocarcinoma cell strains
- St. Jude Children's Research Hospital, Memphis, TN 38105 (United States)
- University of Oslo, Oslo (Norway)
- National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)
- Spectral Genomics Inc., Houston, TX 77054 (United States)
- John Hopkins University, Baltimore, MD 21205 (United States)
- National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)
The incidence of adenocarcinoma of the lung is increasing in the United States, however, the difficulties in obtaining lung cancer families and representative samples of early to late stages of the disease have lead to the study of mouse models for lung cancer. We used Spectral Karyotyping (SKY), mapping with fluorescently labeled genomic clones (FISH), comparative genomic hybridization (CGH) arrays, gene expression arrays, Western immunoblot and real time polymerase chain reaction (PCR) to analyze nine pairs of high-invasive and low-invasive tumor cell strains derived from early passage mouse lung adenocarcinoma cells to detect molecular changes associated with tumor invasion. The duplication of chromosomes 1 and 15 and deletion of chromosome 8 were significantly associated with a high-invasive phenotype. The duplication of chromosome 1 at band C4 and E1/2-H1 were the most significant chromosomal changes in the high-invasive cell strains. Mapping with FISH and CGH array further narrowed the minimum region of duplication of chromosome 1 to 71-82 centimorgans (cM). Expression array analysis and confirmation by real time PCR demonstrated increased expression of COX-2, Translin (TB-RBP), DYRK3, NUCKS and Tubulin-{alpha}4 genes in the high-invasive cell strains. Elevated expression and copy number of these genes, which are involved in inflammation, cell movement, proliferation, inhibition of apoptosis and telomere elongation, were associated with an invasive phenotype. Similar linkage groups are altered in invasive human lung adenocarcinoma, implying that the mouse is a valid genetic model for the study of the progression of human lung adenocarcinoma.
- OSTI ID:
- 21180472
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 233, Issue 1; Conference: 2007 TRAC: 2007 toxicology and risk assessment conference: Emerging issues and challenges in risk assessment, West Chester, OH (United States), 23-26 Apr 2007; Other Information: DOI: 10.1016/j.taap.2008.01.031; PII: S0041-008X(08)00034-3; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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