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

J Natl Cancer Inst. 1997 Dec 17;89(24):1868-74. doi: 10.1093/jnci/89.24.1868.

Abstract

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 G1 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 situ 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 AIDS-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Southern
  • Cyclin D
  • Cyclins / biosynthesis*
  • Cyclins / genetics*
  • DNA Probes
  • DNA, Complementary
  • Gene Expression Regulation, Neoplastic*
  • Gene Expression Regulation, Viral*
  • Herpesvirus 8, Human / genetics*
  • Humans
  • In Situ Hybridization
  • RNA, Messenger
  • RNA, Viral
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / virology*

Substances

  • Cyclin D
  • Cyclins
  • DNA Probes
  • DNA, Complementary
  • RNA, Messenger
  • RNA, Viral