Erk activation as a possible mechanism of transformation of subependymal nodule into subependymal giant cell astrocytoma.

Abstract

Subependymal nodule (SEN) and subependymal giant cell astrocytoma (SEGA) are brain lesions frequently found in tuberous sclerosis (TS). As about 10-15% of SENs enlarge and transform into SEGAs, we examined here the possible mechanism of the phenomenon. Using Western blot we studied 1 SEN and 3 SEGA samples; SEN and 1 SEGA came from the same TS patient. We evaluated e.g. the activation of the phosphorylated forms of proteins belonging to Akt, Erk and mTOR pathways. Differences in Erk pathway activation between SEN and SEGA were found. There was no upregulation of p-Erk, p-Mek or p-RSK1 in the SEN specimen, whilst we found these proteins to be significantly uptriggered in SEGA samples. Also, for the first time, we found p-Akt, p-GSK3 and p-PDK1 upregulated in both SEN and SEGA from the same TS patient. Our current study shows for the first time the possible mechanism of SEN/SEGA transformation, where Erk pathway hyperactivation seems to be significant. We hypothesize that SEN/SEGA transformation may depend on Erk potentiation.