EXPRESSION OF HUMAN-HERPESVIRUS-8-ENCODED CYCLIN-D IN KAPOSIS-SARCOMASPINDLE CELLS

Background: Human herpesvirus 8 (HHV-8) DNA sequences have been detect ed in Kaposi's sarcoma, in primary effusion lymphoma (an unusual high- grade non-Hodgkin's lymphoma seen primarily in patients with acquired immunodeficiency syndrome [AIDS]), and in Castleman's disease (a rare lymphoproliferative disorder); however, proof that HHV-8 is involved i n the pathogenesis of these diseases remains to be established, HHV-8 contains a gene, i.e., v-cyclin D, that is a homologue of the cellular cyclin D2 gene, which encodes a protein that promotes passage through G(1) phase of the cell cycle. Previous studies have identified v-cycl in D messenger RNA (mRNA) in biopsy specimens of Kaposi's sarcoma. In this study, we isolated a full-length v-cyclin D complementary DNA and characterized the pattern of v-cyclin D mRNA expression in Kaposi's s arcoma, Methods: Standard methods were used to construct and to screen HHV-8 genomic and complementary DNA libraries, Reverse transcription- polymerase chain reaction (RT-PCR) methods and in sial hybridization w ith RNA probes were used to examine v-cyclin D mRNA expression, Result s: RT-PCR demonstrated the presence of v-cyclin D mRNA in biopsy speci mens of AIDS-related Kaposi's sarcoma, in early-passage spindle cells from classical (i.e., not ADDS-related) Kaposi's sarcoma, and in spind le cells isolated from the peripheral blood of patients with AIDS-rela ted Kaposi's sarcoma. In situ hybridization indicated that mRNAs for v -cyclin D and kaposin, an HHV-8 latency-associated gene, were present in approximately 1% of the spindle cells in early patch lesions and ap proximately 60% of the spindle cells in late nodular lesions of Kaposi 's sarcoma, Conclusions: Spindle cells of Kaposi's sarcoma, which have been regarded as the tumor cells of this cancer, contain v-cyclin D m RNA. Expression of v-cyclin D protein may be involved in the pathogene sis of Kaposi's sarcoma by promoting cell proliferation.