Proliferation of human melanoma cells is under tight control of protein kinase C alpha.
Exponential proliferation of human melanoma cells has been associated with low levels of protein kinase C (PKC)-alpha. The aim of the present study was to investigate the functional relationship between PKC-alpha and melanoma cell proliferation. Treatment of human melanoma cells with the selective PKC inhibitor Ro-31-8220 resulted in a significant increase of cell proliferation as measured by (3)H-thymidine incorporation and a fluorometric microassay. In addition, phosphorothioate antisense-oligodeoxynucleotides (ODNs) to PKC-alpha enhanced DNA-synthesis of human melanoma cells. Furthermore, microinjection and transient transfection of melanoma cells with PKC-alpha decreased their proliferation, as shown by the reduction of nuclear staining with the proliferation marker Ki-67. The presented data demonstrate a cause-effect relationship between PKC-alpha and melanoma cell growth, whereby PKC-alpha reversely influences the rate of cell proliferation.
Krasagakis
Konstantin
K
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Berlin, Germany. krasagak@med.uoc.gr
Lindschau
Carsten
C
Fimmel
Sabine
S
Eberle
Jürgen
J
Quass
Petra
P
Haller
Hermann
H
Orfanos
Constantin E
CE
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008545:Melanoma / Q000201:enzymology*; D008845:Microinjections; D018613:Microscopy, Confocal; D020319:Oligodeoxyribonucleotides, Antisense; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D051571:Protein Kinase C-alpha; D014162:Transfection
D004791:Enzyme Inhibitors; D007211:Indoles; D020319:Oligodeoxyribonucleotides, Antisense; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C064758:Ro 31-8220