These results provide evidence that cis activation of the basal promoter of the human PKCalpha gene occurs through an AP-2-dependent, phorbol ester-responsive pathway, which suggests an autoregulatory manner of transcription in GBM.
Treatment of a panel of established GBM cell lines (U138MG, U87, U373 and C6) with pharmacological NFκB inhibitors (BAY117082, parthenolide, MG132, curcumin and arsenic trioxide) and NFκB-p65 siRNA markedly decreased the viability of GBMs as compared to inhibitors of other signaling pathways such as MAPKs (ERK, JNK and p38), PKC, EGFR and PI3K/Akt.
A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings.
In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation.
We found that LPA<sub>1</sub> induces PKCα translocation to the nucleus, but not to the cell membrane after LPA treatment and the cell number diminished when LPA<sub>1</sub>/PKCα signaling was blocked, suggesting a relevant role of LPA<sub>1</sub> and PKCα in GBM growth.