Expression of human herpesvirus 8-encoded cyclin D in Kaposi's sarcoma spindle cells.
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.
Davis
M A
MA
Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Stürzl
M A
MA
Blasig
C
C
Schreier
A
A
Guo
H G
HG
Reitz
M
M
Opalenik
S R
SR
Browning
P J
PJ
D015139:Blotting, Southern; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics*; D015342:DNA Probes; D018076:DNA, Complementary; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D012333:RNA, Messenger; D012367:RNA, Viral; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000821:virology*
D056741:Cyclin D; D016213:Cyclins; D015342:DNA Probes; D018076:DNA, Complementary; D012333:RNA, Messenger; D012367:RNA, Viral