Expression of human herpesvirus 8-encoded cyclin D in Kaposi's sarcoma spindle cells

被引:112
作者
Davis, MA
Stürzl, M
Blasig, C
Schreier, A
Guo, HG
Reitz, M
Opalenik, SR
Browning, PJ
机构
[1] Vanderbilt Univ, Sch Med, Div Med Oncol, Dept Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Dept Cell Biol, Nashville, TN 37232 USA
[3] Max Planck Inst Biochem, Dept Virus Res, D-82152 Martinsried, Germany
[4] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA
关键词
D O I
10.1093/jnci/89.24.1868
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Human herpesvirus 8 (HHV-8) DNA sequences have been detected 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 in 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-cyclin 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 sarcoma, 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 with RNA probes were used to examine v-cyclin D mRNA expression, Results: RT-PCR demonstrated the presence of v-cyclin D mRNA in biopsy specimens of AIDS-related Kaposi's sarcoma, in early-passage spindle cells from classical (i.e., not ADDS-related) Kaposi's sarcoma, and in spindle cells isolated from the peripheral blood of patients with AIDS-related 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 approximately 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 mRNA. Expression of v-cyclin D protein may be involved in the pathogenesis of Kaposi's sarcoma by promoting cell proliferation.
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页码:1868 / 1874
页数:7
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