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Anticancer Res. 2009 Jan;29(1):119-23.

Rho/ROCK and MAPK signaling pathways are involved in glioblastoma cell migration and proliferation.

Author information

1
Department of Neurosurgery, New York Medical College, Valhalla, New York 10595, USA.

Abstract

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.

PMID:
19331140
[Indexed for MEDLINE]
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