Human melanoma metastasis is inhibited following ex vivo treatment with an antisense oligonucleotide to protein kinase C-alpha.
To determine whether alteration of PKC alpha expression would affect the metastatic potential of human melanoma cells, replicate cultures of C8161 cells were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161 cultures were treated with a scrambled sequence ODN, cationic liposomes or were left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75% when ISIS-3521-treated cells were injected intravenously into athymic mice. These results show that PKC alpha expression is important in the regulation of human melanoma metastasis.
Dennis
J U
JU
Department of Comparative Medicine, The Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
Dean
N M
NM
Bennett
C F
CF
Griffith
J W
JW
Lang
C M
CM
Welch
D R
DR
D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary; D008545:Melanoma / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D012313:RNA / Q000032:analysis; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D012313:RNA; C496628:PRKCA protein, human; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha