Non-Random Chromosomal Changes in High- and Low-Invasive Tumor Cells Derived from Early Passage Mouse Lung Adenocarcinoma Cell Strains

Details

• Personal Author:
  David LT ; Ensell MX ; Jefferson AM ; Johnson RC ; Kashon ML ; Ostvold AC ; Reynolds SH ; Sargent LM ; Senft JR ; Tyson FL
• Description:
  The incidence of adenocarcinoma is increasing in the United States, however, the difficulty in obtaining lung cancer families and representative samples of early to late stages of the disease have lead to the study of mouse models. We used a battery of tests to detect molecular changes associated with tumor invasion. Spectral karyotyping, mapping with fluorescently labeled genomic clones, comparative genomic hybridization arrays, expression arrays, Western blot and real time polymerase chain reaction (PCR) were used to analyze nine pairs of high invasive and low invasive tumor cell strains derived from early passage lung adenocarcinoma cell strains. The duplication of chromosome 1 and 15 and deletion of chromosome 8 were significant in high invasive cultures compared to low invasive cultures. The duplication of chromosome 1 between bands E2 and H1 was the most significant chromosomal change in the invasive cell strains. Mapping with fluorescent in situ hybridization and comparative genomic hybridization (CGH) array further narrowed the minimum region of duplication of chromosome 1 to 71 to 82 centimorgans (cM) as well as three deleted regions from 67-69 cM, 84-84 cM and 100-110 cM. Analysis of an expression array and confirmation by real time PCR identified increased expression of genes that were associated with the invasive phenotype. The amplified copy number and expression of vacuolar protein sorting 4B (SKD1), translin, and DYRK3 were significantly elevated in the invasive cell strains at p<0.00001. The copy number of NUCKS and tubulin a-4 showed a trend for increased expression in the cell strains that were able to invade a gel matrix. The increased copy number and expression of genes involved in cell movement, proliferation, and inhibition of apoptosis were associated with the invasive phenotype. The homologous linkage groups on human chromosomes 1q32-41, 2q, 8q24 and 8p are altered in invasive human lung cancer. Increased copy number and expression of the genes on mouse chromosome 1 may play a functional role in lung cancer development and may aid in the identification of mouse and human lung cancer susceptibility genes. [Description provided by NIOSH]
• Subjects:
  Animals Chromosomes Genetics Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Animal-studies Cancer Cancer-rates Chromosome-damage Chromosome-disorders Genetic-factors Laboratory-animals Lung-cancer Models Pulmonary-system-disorders Respiratory-system-disorders

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• ISSN:
  0197-016X
• Publisher:
  American Association for Cancer Research
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  47
• NIOSHTIC Number:
  nn:20031306
• Citation:
  97th AACR Annual Meeting, April 1-5, 2006, Washington D.C. Philadelphia, PA: American Association for Cancer Research, 2006 Apr; 47:1201
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  False
• Source Full Name:
  97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington D.C.
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cf493c8f52d8ead1b609fd10e3f2f10a9c0fdcb0aef066b38eafd2e2ed6b44e07b28cdc2639f4dc8bf164142291d674ed1fa1eab65a27d88c329eee3f9cf7680
• Download URL:
  https://stacks.cdc.gov/view/cdc/191599/cdc_191599_DS1.pdf
• File Type:
  [PDF - 684.59 KB ]