The algorithm measured significant increase in F-actin at cell edges with concomitant decrease in internal punctate actin in astrocytoma cells lacking functional neurofibromin and p53 when treated with three structurally-distinct anticancer small molecules: OSW1, Schweinfurthin A (SA) and a synthetic marine compound 23'-dehydroxycephalostatin 1.
Analyzed astrocytomas without mutations in Ras or neurofibromin may harbor mutations in other proteins of this pathway leading to hyperactive Ras signaling.
However, no methylation was found at the NF1 promoter region in PA. To rule out that silencing of NF1 by promoter methylation is restricted to higher-grade astrocytomas, 15 pediatric WHO II degree and IV degree astrocytomas were analyzed: 12 astrocytomas II and 3 glioblastomas displayed no NF1 promoter methylation.
Collectively, our results suggest that loss of neurofibromin is not sufficient for astrocytoma formation in mice and that other genetic or environmental factors might influence NF1-associated glioma tumorigenesis.
Impaired neurofibromin function in these nervous system cells contributes to the development of astrocytomas, learning disabilities, and radiographic abnormalities of the brain.
Furthermore, when levels of activated p21 ras were decreased in astrocytoma cells expressing the ras inhibitory Asn-17 dominant-negative mutant, levels of neurofibromin expression decreased.