Differential role for protein kinase C-mediated signaling in the proliferation of medulloblastoma cell lines.
Recent studies have implicated protein kinase C (PKC)-mediated signaling in the proliferation of gliomas. In this study, we have investigated the role of PKC mediated signaling in the proliferation of medulloblastoma cell lines DAOY, D283-Med and D341-Med. By Western blot analyses, conventional PKC (cPKC) alpha was detectable in DAOY only, while atypical PKC (aPKC) zeta was present in all three cell lines. cPKC beta1, beta11, gamma novel PKC (nPKC) delta, and epsilon were not detectable in any of the cell lines. Antisense oligonucleotides to PKC alpha , Calphostin C (a specific PKC inhibitor) and prolonged treatment with phorbol 12-myristate 13-acetate (PMA) with down regulation of cPKCalpha caused a decrease in proliferation in DAOY and no effect on D283-Med. Furthermore, PMA treatment was also associated with upregulation of p21cip1 in DAOY. Since cPKCalpha is the only PMA responsive isoform in DAOY, this observation implicates the cPKCalpha isoform in the proliferation of DAOY but not in D283-Med. A comparison of DAOY and D283-Med showed a higher proliferation index in DAOY. In contrast, multiprobe riboquant ribonuclease protection assay revealed higher levels of p27kip1 and p21cip1 mRNA in D283-Med. These transcripts were barely detectable in untreated DAOY. These observations indicate possible significant molecular heterogeneity among medulloblastomas with implications for differing biology among medulloblastoma cell lines and tumors.
Adesina
A M
AM
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Dooley
N
N
Yong
V W
VW
Nalbantoglu
J
J
D002455:Cell Division; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008527:Medulloblastoma / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D012333:RNA, Messenger; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate