TY - JOUR T1 - Rho/ROCK and MAPK Signaling Pathways Are Involved in Glioblastoma Cell Migration and Proliferation JF - Anticancer Research JO - Anticancer Res SP - 119 LP - 123 VL - 29 IS - 1 AU - VAHE MICHAEL ZOHRABIAN AU - BRIAN FORZANI AU - ZELING CHAU AU - RAJ MURALI AU - MEENA JHANWAR-UNIYAL Y1 - 2009/01/01 UR - http://ar.iiarjournals.org/content/29/1/119.abstract N2 - Background: Glioblastoma multiforme (GBM) remains the most aggressive and frequently occurring brain neoplasm. Members of the Rho family of small GTP-binding proteins, including Rho, Rac, and Cdc42, have been shown to participate in cell growth differentiation and motility. The mitogen-activated protein kinase (MAPK) pathway, which includes extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), has been shown to regulate cell growth, differentiation and motility. Here, the involvement of the Rho and Rho-associated protein kinase (ROCK) pathway, along with MAPK, was investigated to determine their roles in GBM cell migration and proliferation. Materials and Methods: In vitro studies utilized the human malignant glioblastoma cell line LN-18. The cells were treated with Y-27632, a ROCK inhibitor, and U0126, an upstream MAPK kinase inhibitor (MEK), alone or in combination with one another. Immunoblotting analysis established the levels of phosphorylated ERK1/2. Cell migration was determined by radial migration assay and cell proliferation by MTT. Results: Y-27632 reduced phosphorylation of ERK1/2 at 0.5 and 2 h. U0126 in combination with Y-27632 led to a more pronounced repression of platelet-derived growth factor (PDGF)- or fibronectin (FN)-induced ERK1/2 activation than U0126 treatment alone. Y-27632 treatment for 24 h suppressed GBM cell migration and resulted in a reduction in LN-18 cell proliferation. Furthermore, PDGF and FN-induced cell proliferation was suppressed by pre-treatment with Y-27632 or U0126, with the greatest reduction achieved by a combination of the two inhibitors. Conclusion: Rho/ROCK signaling is involved in GBM cell migration and proliferation, and this pathway may be linked to ERK signaling. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -