Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Chromosomal changes in high- and low-invasive mouse lung adenocarcinoma cell strains derived from early passage mouse lung adenocarcinoma cell strains.

Authors
Sargent-LM; Ensell-MX; Ostvold-AC; Baldwin-KT; Kashon-ML; Lowry-DT; Senft-JR; Jefferson-AM; Johnson-RC; Li-Z; Tyson-FL; Reynolds-SH
Source
Toxicol Appl Pharmacol 2008 Feb; 233(1):81-91
NIOSHTIC No.
20034751
Abstract
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-a4 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.
Keywords
Toxins; Particulate-dust; Dust-inhalation; Dust-exposure; Pulmonary-congestion; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Lung-disorders; Lung-irritants; Laboratory-animals; Laboratory-testing; Aerosol-particles; Cell-biology; Cell-function; Cellular-function; Cellular-respiration; Genes; Genetic-factors; Genetics; Author Keywords: Mouse model; Lung adenocarcinoma; Amplification; Chromosome 1; CGH array
Contact
Amy M. Senfta, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Health Effects Laboratory Division, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
TXAPA9
Publication Date
20080201
Document Type
Journal Article
Email Address
LSargent@cdc.gov
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0041-008X
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicology and Applied Pharmacology
State
WV; MD; TN; NC
TOP