Cell size and proliferation of subependymal giant cell astrocytomas are regulation by mTOR ans Ras-ERK signaling pathway

• Autorzy: Tyburczy M. , Kotulska K. , Jozwiak S. , Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Tuberous sclerosis complex (TSC) is characterized by cortical developmental malformations that are associated with epilepsy and appearance of benign brain tumors – subependymal giant cell astrocytomas (SEGAs) which are composed of distinct cell types, including giant cells and dysplastic neurons. TSC results from mutations in TSC1 and TSC2, which lead to the mTOR pathway activation, and p70S6 kinase and ribosomal S6 protein phosphorylation. ERK pathway is also aberrantly activated in SEGAs. Clinical trials with the mTOR inhibitor – rapamycin have demonstrated reduction in size of SEGAs, but the molecular mechanisms are unknown. In the present study, we evaluated the effects of rapamycin and the ERK pathway inhibitor – UO126 on cell size, proliferation and viability of cell cultures derived from SEGA. Rapamycin or UO126 alone did not affect viability and proliferation of SEGA cells. However, treatment with both drugs reduced proliferation of SEGA cells. Staining of F-actin revealed decrease of cell size in SEGA cultures exposed to rapamycin alone or in combination with UO126, but treatment with UO126 alone did not infl uence cell size nor morphology. Our studies demonstrate that simultaneous inhibition of both mTOR and ERK signaling pathways reduces proliferation of SEGA cells. Moreover, inhibition of mTOR signaling with rapamycin diminishes a volume of giant SEGA cells. It implicates that inhibitors of mTOR and ERK pathways should be considered for clinical trials of SEGAs.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.346-347

Twórcy

autor

Tyburczy M.

• Department of Cell Biology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Kotulska K.

• Department of Pediatric Neurology, The Children's Memorial Health Institute, Warsaw, Poland

autor

Jozwiak S.

• Department of Pediatric Neurology, The Children's Memorial Health Institute, Warsaw, Poland

autor

Kaminska B.

• Department of Cell Biology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland