Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells

Details

• Personal Author:
  Dinu C-Z ; Lohcharoenkal W ; Park J ; Rohanasakul Y ; Stueckle, Todd A. ; Tse W ; Wang L
• Description:
  Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2. Downregulation of H-Ras by siRNA or inactivation of ERK by chemical inhibitor effectrively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epitheial-mesenchymal transition (EMT) transcriptional regulators, were up-regulated in the SWCNT-exposed cells, suggesting their role in the aggressive phenotype. Cortactin expression was shown to be controlled by the H-Ras/ERK signaling. Thus, our results indicate a novel role of H-Ras/ERK signaling and cortactin in the aggressive transformation of human mosethelial cells by SWCNT. [Description provided by NIOSH]
• Subjects:
  Carcinogens Hazardous Substances Nervous System Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Author Keywords: Mesothelial Cells Biomedical-engineering Cell-function Cell Transformation Cellular-function Cortactin ERK Exposure-levels H-Ras Health-hazards Humans Mesothelial-cells Nanotechnology Neoplastic-transformation Risk-factors SWCNT

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• ISSN:
  1664-042X
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  5
• NIOSHTIC Number:
  nn:20044593
• Citation:
  Front Physiol 2014 Jun; 5:222
• Contact Point Address:
  Yon Rojanasakul, Department of Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, 5706 Medical Center Dr., Morgantown, WV 26506
• Email:
  yrojan@hsc.wvu.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Frontiers in Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a2534a19562cb70fc5826be56ab515421740d390c427e93302ea4ca1cb39c90d645af5e13254019acc2b6ae4fcd4ab399e274fe0fe85889534d32fe97bf5df4d
• Download URL:
  https://stacks.cdc.gov/view/cdc/200262/cdc_200262_DS1.pdf
• File Type:
  [PDF - 1.26 MB ]