In vitro and in vivo tumor growth suppression by HIV-1 Vpr.
We have previously reported that the human immunodeficiency virus type 1 (HIV-1) regulatory gene vpr induces differentiation of rhabdomyosarcoma (embryonal muscle tumor cell line) cells, an effect that is accompanied by reduced proliferative capacity of the transfected cells. In this report, we examine the effect of Vpr expression on several different tumor cell lines derived from unique lineages. These tumor cells display different patterns of modulated oncogenes including both ras and p53 mutations. Here we demonstrate that the growth of tumor cells in vitro and in vivo is arrested by the expression of HIV-1 Vpr. Expression of Vpr in several human tumor cell lines upon transfection resulted in an accumulation of cells in the G2/M phase of cell cycle with altered cellular morphology, including an increase in adherence, and growth arrest, consistent with a differentiated phenotype. Vpr expression in B78/H1 cells results in a marked reduction in colony formation in vitro and an associated reduction in melanin synthesis by the cells. Vpr-transfected melanoma cells inoculated into syngenic C57BL/6 mice showed a markedly reduced ability to form tumors in vivo. These results suggest that this retroviral regulatory gene has broad tumor suppressor effects, likely mediated by transcriptional regulation of the state of the host cell.
Mahalingam
S
S
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612, USA.
MacDonald
B
B
Ugen
K E
KE
Ayyavoo
V
V
Agadjanyan
M G
MG
Williams
W V
WV
Weiner
D B
DB
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D005347:Fibroblasts; D015870:Gene Expression; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D015497:HIV-1; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008543:Melanins / Q000096:biosynthesis; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D009857:Oncogenes; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D008543:Melanins; D054325:vpr Gene Products, Human Immunodeficiency Virus