Autoinduction of platelet derived growth factor (PDGF) A-chain mRNA expression in a human malignant melanoma cell line and growth inhibitory effects of PDGF-A-chain mRNA-specific antisense molecules.
Autoinduction of PDGF-A-chain mRNA's was demonstrated in cells of a human malignant melanoma cell line (HTZ 19), indicating a PDGF-induced amplification of an autocrine growth factor loop mechanism. PDGF-alpha receptors were detected by immunocytochemistry in HTZ 19 melanoma cells. Exogenously administered PDGF-AA exerted an increase in cell proliferation by 70% at 200 ng/ml PDGF in serum-supplemented cell culture medium. Antisense phosphorothioate-oligodeoxynucleotides (S-ODN's), specifically targeted against PDGF-A-chain mRNA, reduced cell proliferation of HTZ 19 melanoma cells by 62% at a concentration of 5.0 microM, also only in serum-enriched medium. These findings strongly suggest that PDGF-AA homodimers may be an autocrine growth factor for HTZ 19 melanoma cells but require synergistic interaction with serum components.
Department of Neurology, University of Wuerzburg, Germany.
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Behl
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Bogdahn
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Winkler
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Apfel
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Brysch
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Schlingensiepen
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D046911:Macromolecular Substances; D008545:Melanoma; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D016372:RNA, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D016372:RNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013873:Thionucleotides; D017479:Receptors, Platelet-Derived Growth Factor