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Human Immunodeficiency Virus-l Tat Positively Regulates the Human CD99 Gene via DNA Demethylation  

Lee, Eu-Gene (Department of Biological Sciences, Konkuk University)
Kim, Ye-Ri (Department of Biological Sciences, Konkuk University)
Lee, Mi-Kyung (Department of Biological Sciences, Konkuk University)
Lee, Im-Soon (Department of Biological Sciences, Konkuk University)
Publication Information
Korean Journal of Microbiology / v.44, no.4, 2008 , pp. 277-281 More about this Journal
Abstract
HIV affects many organ systems. Patients with HIV infection have substantially increased risk of developing various cancers, primarily by opportunistic infection with oncogenic viruses due to their immunocompromised status. However, extensive evidence also indicates that the viral protein, Tat itself, may playas a major factor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Therefore, in this study, we examined the effect of HIV-l Tat on CD99 as one of the target cellular genes, which is a well-known tumor marker in several cancers. By using established HeLa clones that are stably expressing Tat, we found that CD99 is upregulated by endogenous Tat, whereas STAT3 is down regulated. Upon the screening of genes differentially expressed between Tat-stable cells and the control cells by using the gene fishing technique, DEG, we detected 3 genes which expression is affected by the presence of Tat. Furthermore, the methylation specific PCR analysis of the stably Tat expressing cell lines revealed that the CD99 promoter is de methylated in the presence of Tat. Taken together, these results open a potential role of CD99 in AIDS-related oncogenesis via epigenetic regulation by HIV-1 Tat.
Keywords
CD99 promoter; CpG island; HIV-1-Tat; methylation;
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1 Goedert, J.J., T.R. Cote, P. Virgo, S.M. Scoppa, D.W. Kingma, M.H. Gail, E.S. Jaffe, and R.J. Biggar. 1998. Spectrum of AIDSassociated malignant disorders. Lancet 351, 1833-1839   DOI   ScienceOn
2 Lee, M.K., S.H. Park, and I.S. Lee. 2008. DNA methylation dependent regulation of human CD99 expression in HRS cells of Hodgkin's lymphoma. Korean J. Genetic 30, 73-82
3 Emerman, M., H. Micheal, and M. Malim. 1998. HIV-1 regulatory/ accessory genes : Keys to unraveling viral and host cell biology. Science 280, 1880-1884   DOI   ScienceOn
4 Corallini, A., R. Sampaolesi, L. Possati, M. Merlin, P. Bagnarelli, C. Piola, M. Fabris, M.A. Menegatti, S. Talevi, D. Gibellini, R. Rocchetti, A. Caputo, and G. Barbanti-Brodano. 2002. Inhibition of HIV-1 Tat activity correlates with down-regulation of bcl-2 and results in reduction of angiogenesis and oncogenicity. Virology 299, 1-7   DOI   ScienceOn
5 Verhoef, K., M. Tijms, and B. Berkhout. 1997. Optimal Tat-mediated activation of the HIV-1 LTR promoter requires a full-length TAR RNA hairpin. Nucleic Acids Res. 25, 496-502   DOI
6 Aboulafia, D.M., M. Meneses, S. Ginsberg, M.S. Siegel, W.W. Howard, and B.J. Dezube. 2000. Acute myeloid leukemia in patients infected with HIV-1. AIDS 16, 865-876   DOI   ScienceOn
7 Marlo, A. and J.G. Herman. 1995. CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/ CDKN2/MTS1 in human cancers. Nat. Med. 1, 686-692   DOI
8 McArthur, C.P., Y. Wang, D. Heruth, and S. Gustafson. 2001. Amplification of extracellular matrix and oncogenes in tat-transfected human salivary gland cell lines with expression of laminin, fibronectin, collagens I, III, IV, c-myc and p53. Arch. Oral Biol. 46, 545-555   DOI   ScienceOn
9 Robert, M.F., S. Morin, N. Beaulieu, F. Gauthier, I.C. Chute, A. Barsalou, and A.R. MacLeod. 2002. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat. Genet. 33, 61-65   DOI   ScienceOn
10 Brierley, M.M., N. Eleanor, and A. Fish. 2005. STATs : Multifaceted regulators of transcription. J. Interf. Cytok. Res. 25, 733-744   DOI   ScienceOn
11 Zhang, Q., H.Y. Wang, A. Woetmann, P.N. Raghunath, N. Odum, and M.A. Wasik. 2006. STAT3 induces transcription of DNA methyltransferase 1 (DNMT1) gene in malignant T-lymphocytes. Blood 108, 1058-1064   DOI   ScienceOn
12 Blazquez, M.V., A. Macho, C. Ortiz, C. Lucena, M. Lopez-Cabrera, F. Sanchez-Madrid, and E. Munoz. 1999. Extracellular HIV type 1 Tat protein induces CD69 expression through NF-kB activation : Possible correlation with cell surface Tat-binding proteins. AIDS Res. Hum. Retrov. 15, 1209-1218   DOI   ScienceOn
13 Huynh, D., E. Vincan, T. Mantamadiotis, D. Purcell, C.K. Chan, and R. Ramsay. 2007. Oncogenic properties of HIV-Tat in colorectal cancer cells. Curr. HIV Res. 5, 403-409   DOI
14 Kadin, M.E. 1994. Pathology of Hodgkin's disease. Curr. Opin. Oncol. 6, 456-463   DOI
15 Ensoli, B., L. Buonaguro, G. Barillari, V. Fiorelli, R. Gendelman, R.A. Morgan, P. Wingfield, and R.C. Gallo. 1993. Release, uptake, and effects of extracellular Human Immunodeficiency Virus type I Tat protein on cell growth and viral transactivation. J. Virol. 67, 277-287   PUBMED
16 Farrell, P.J., I. Cludts, and A. Stuhler. 1997. Epstein-Barr virus genes and cancer cells. Biomed. Pharmacother. 51, 58-67   DOI   ScienceOn
17 Serraino, D., P. Pezzotti, M. Dorrucci, M.B. Alliegro, A. Sinicco, and G. Rezza. 1997. Cancer incidence in a cohort of HIV seroconverters. HIV Italian Seroconversion Study Group. Cancer 79, 1004-1008   DOI   ScienceOn
18 Evans, T.J., M.G. Jacquemin, and P.J. Farrell. 1995. Efficient EBV superinfection of group 1 Burkitt's lymphoma cells distinguishes requirements for expression of the Cp viral promoter and can activate the EBV productive cycle. Virology 206, 866-877   DOI   ScienceOn
19 Fittipaldi, A. and M. Giacca. 2005. Transcellular protein transduction using the Tat protein of HIV-1. Adv. Drug Deliver. Rev. 57, 597-608   DOI   ScienceOn
20 Sohn, H.W., E.Y. Choi, S.H. Kim, I.S. Lee, D.H. Chung, U.A. Sung, D.H. Hwang, S.S. Cho, B.H. Jun, J.J. Jang, J.G. Chi, and S.H. Park. 2001. CD99 regulates the transport of MHC class I molecules from the golgi complex to the cell surface. J. Immunol. 166, 787-794   DOI   PUBMED