| 2 | Human immunodeficiency virus type 1 tat accelerates kaposi sarcoma-associated herpesvirus kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice显示文摘Kaposi sarcoma-associated herpesvirus(KSHV) is necessary but not sufficient to cause Kaposi sarcoma(KS).Coinfection with human immunodeficiency virus type 1(HIV-1), in the absence of antiretroviral suppressive therapy, drastically increases the risk of KS.Previously, we identified that HIV-1 transactivative transcription protein(Tat) was an important cofactor that activated lytic cycle replication of KSHV.Here, we further investigated the potential of Tat to influence tumorigenesis induced by KSHV Kaposin A, a product of KSHV that was encoded by the open reading frame K12(a KSHV-transforming gene).By using colony formation in soft agar, H-3-TdR incorporation, cell cycle, and microarray gene expression analyses, we demonstrated that Tat enhanced proliferation as well as mitogen-activated protein kinase, signal transducer and activator of transcription 3, and phosphatidylinositol 3-kinase/protein kinase B signaling induced by Kaposin A in NIH3T3 cells.Animal experiments further demonstrated that Tat accelerated tumorigenesis by Kaposin A in athymic nu/nu mice.Cells obtained from primary tumors of nude mice succeeded inducing tumors in immunocompetent mice.These data suggest that Tat can accelerate tumorigenesis induced by Kaposin A.Our data present the first line of evidence that Tat may participate in KS pathogenesis by collaborating with Kaposin A in acquired immunodeficiency syndrome(AIDS)-related KS(AIDS-KS) patients.Our data also suggest that the model for Kaposin and Tat-mediated oncogenesis will contribute to our understanding of the pathogenesis of AIDS-KS at the molecular level and may even be important in exploring a novel therapeutic method for AIDS-KS. | Chen, Xiuying Cheng, Lin Jia, Xuemei Yao, Shuihong Lv, Zhigang Qin, Di Fang, Xin Lu, Chun Nanjing Med Univ, Dept Microbiol & Immunol, Nanjing 210029, Peoples R China.Chen, Xiuying Lu, Chun Nanjing Med Univ, Lab Reprod Med, Nanjing 210029, Peoples R China.Chen, Xiuying Lu, Chun Nanjing Med Univ, Key Lab Pathogen Biol Jiangsu Prov, Nanjing 210029, Peoples R China.Chen, Xiuying Lu, Chun Key Lab Lab Med Jiangsu Prov, Nanjing 210029, Peoples R China.Chen, Xiuying Lei, Yongliang Lishui Ctr Dis Control & Prevent, Lishui 323000, Zhejiang, Peoples R China.Cheng, Lin Huanghe Sci & Technol Coll, Dept Microbiol & Immunol, Zhengzhou 450006, Peoples R China.Zeng, Yi Youjiang Med Coll Nationalities, Dept Microbiol & Immunol, Bose 533000, Peoples R China. | 2010 | 南京医科大学学报(自然科学版)2010，30，1： | 1 |
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