title: Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells.
abstract: 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 effectively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epithelial-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 mesothelial cells by SWCNT.
authors: Department of Pharmaceutical Sciences, West Virginia University Morgantown, WV, USA.
authors: Warangkana
authors: W
authors: Lohcharoenkal
authors: Health Effects Laboratory Division, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health Morgantown, WV, USA.
authors: Liying
authors: L
authors: Wang
authors: Health Effects Laboratory Division, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health Morgantown, WV, USA.
authors: Todd A
authors: TA
authors: Stueckle
authors: Department of Medicine, Mary Babb Randolph Cancer Center, West Virginia University Morgantown, WV, USA.
authors: Jino
authors: J
authors: Park
authors: Department of Medicine, Mary Babb Randolph Cancer Center, West Virginia University Morgantown, WV, USA.
authors: William
authors: W
authors: Tse
authors: Department of Chemical Engineering, West Virginia University Morgantown, WV, USA.
authors: Cerasela-Zoica
authors: CZ
authors: Dinu
authors: Department of Pharmaceutical Sciences, West Virginia University Morgantown, WV, USA ; Department of Medicine, Mary Babb Randolph Cancer Center, West Virginia University Morgantown, WV, USA.
authors: Yon
authors: Y
authors: Rojanasakul
keywords: ERK; H-Ras; SWCNT; cell transformation; cortactin; mesothelial cells