PMID- 12743275 OWN - NLM STAT- MEDLINE DCOM- 20030612 LR - 20190508 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 77 IP - 11 DP - 2003 Jun TI - Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells. PG - 6188-96 AB - Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen (LANA) and k-cyclin (kCYC). To assess the oncogenic potential of LANA and kCYC, primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen (LTAg). Interestingly, LANA-transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean +/- standard deviation, 38.3 +/- 11.0 passages) than untransduced cells and vector-transduced cells (<20 passages). By contrast, kCYC-transduced HUVEC did not proliferate faster or live longer than control cells. LANA- and kCYC-transduced HUVEC, but not LTAg-transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA- and kCYC-transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg-transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA-transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA-expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion. FAU - Watanabe, Takahiro AU - Watanabe T AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. FAU - Sugaya, Makoto AU - Sugaya M FAU - Atkins, April M AU - Atkins AM FAU - Aquilino, Elisabeth A AU - Aquilino EA FAU - Yang, Aparche AU - Yang A FAU - Borris, Debra L AU - Borris DL FAU - Brady, John AU - Brady J FAU - Blauvelt, Andrew AU - Blauvelt A LA - eng PT - Journal Article PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, Viral) RN - 0 (Cyclin D) RN - 0 (Cyclins) RN - 0 (Nuclear Proteins) RN - 0 (Proteins) RN - 0 (latency-associated nuclear antigen) SB - IM MH - 3T3 Cells MH - Animals MH - Antigens, Viral MH - Cell Division MH - Cell Transformation, Viral MH - Cyclin D MH - Cyclins/genetics/metabolism MH - Endothelium, Vascular/*cytology MH - Female MH - Herpesvirus 8, Human/metabolism/*pathogenicity MH - Humans MH - Mice MH - Mice, Nude MH - Neovascularization, Physiologic MH - Nuclear Proteins/genetics/*metabolism MH - Oligonucleotide Array Sequence Analysis MH - Proteins/metabolism MH - Sarcoma, Kaposi/*physiopathology/virology MH - *Transduction, Genetic MH - Umbilical Veins PMC - PMC155023 EDAT- 2003/05/14 05:00 MHDA- 2003/06/13 05:00 PMCR- 2003/06/01 CRDT- 2003/05/14 05:00 PHST- 2003/05/14 05:00 [pubmed] PHST- 2003/06/13 05:00 [medline] PHST- 2003/05/14 05:00 [entrez] PHST- 2003/06/01 00:00 [pmc-release] AID - 2457 [pii] AID - 10.1128/jvi.77.11.6188-6196.2003 [doi] PST - ppublish SO - J Virol. 2003 Jun;77(11):6188-96. doi: 10.1128/jvi.77.11.6188-6196.2003.