Consensus-interferon and platelet-derived growth factor adversely regulate proliferation and migration of Kaposi's sarcoma cells by control of c-myc expression.
Platelet-derived growth factor-B (PDGF-B) is a potent paracrine-acting mitogen in Kaposi's sarcoma (KS) lesions. Interferon-alpha is widely used for clinical treatment of KS. Here we show that platelet-derived growth factor-B activates proliferation and migration of cultivated AIDS-KS spindle cells whereas interferon-alpha acts as an inhibitor. At the molecular level, these opposite activities of platelet-derived growth factor-B and interferon-alpha converged onto the adverse regulation of the c-myc gene expression. Platelet-derived growth factor-B induced c-myc mRNA and protein synthesis in cultivated AIDS-KS spindle cells whereas interferon-alpha inhibited these processes. Using c-myc-specific phoshothioate antisense oligodeoxynucleotides, we demonstrated that down-regulation of c-myc expression is sufficient to inhibit proliferation and migration of KS spindle cells in vitro. This indicated that c-Myc protein may be an important regulatory molecule of KS spindle cell proliferation and migration. High amounts of the c-Myc protein were detected in the nuclei of KS spindle cells in histological sections of AIDS-KS biopsies. This suggested that the c-myc gene may also regulate proliferation and migration of AIDS-KS spindle cells in vivo. In this case, c-myc may play an important role in the focus of major pathogenic and therapeutic pathways of KS.
Köster
R
R
Abteilung Virusforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Blatt
L M
LM
Streubert
M
M
Zietz
C
C
Hermeking
H
H
Brysch
W
W
Stürzl
M
M
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D016384:Consensus Sequence; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D010982:Platelet-Derived Growth Factor; D016271:Proto-Oncogene Proteins c-myc; D016222:Fibroblast Growth Factor 2