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American Journal of Pathology, Vol 149, 1871-1885, Copyright © 1996 by American Society for Investigative Pathology

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Consensus-interferon and platelet-derived growth factor adversely regulate proliferation and migration of Kaposi's sarcoma cells by control of c-myc expression

R Koster, LM Blatt, M Streubert, C Zietz, H Hermeking, W Brysch and M Sturzl
Abteilung Virusforschung, Max-Planck-Institut fur Biochemie, Martinsried, Germany.

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.

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