Induction of Transformation by Freshly Fractured Silica in JB6 and BEAS-2B Cells

Silica particles are considered to be fibrogenic agents and established carcinogens, but the mechanisms for disease initiation and progression are not well understood. Earlier studies demonstrated that the tumor suppressor gene, PDCD4, and its upstream regulator, miR-21, may be considered as oncogenes for novel cancer prevention or anti-cancer therapies. The present study examined whether freshly fractured silica particles induce cell transformation. The data indicated that chronically exposed human lung epithelial BEAS-2B or JB6 cells to low-dose silica resulted in neoplastic transformation assayed by soft agar. The alterations of miR-21-PDCD4 signaling in JB6 cells after exposure to freshly fractured silica particles were also tested. The results demonstrate that silica caused PDCD4 inhibition in JB6 cells, exposure of cells to silica caused a significant increase of miR-21 expression and decrease of PDCD4 expression, inhibition of phosphorylated ERKs or phosphorylated p38 with U0126 or SB 203580 revers...