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.
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.
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.
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.
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.