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
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 tr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-12-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558609800961 |
| _version_ | 1811259258926268416 |
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| author | Xiuying Chen Lin Cheng Xuemei Jia Yi Zeng Shuihong Yao Zhigang Lv Di Qin Xin Fang Yongliang Lei Chun Lu |
| author_facet | Xiuying Chen Lin Cheng Xuemei Jia Yi Zeng Shuihong Yao Zhigang Lv Di Qin Xin Fang Yongliang Lei Chun Lu |
| author_sort | Xiuying Chen |
| collection | DOAJ |
| description | 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, 3H-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. |
| first_indexed | 2024-04-12T18:27:46Z |
| format | Article |
| id | doaj.art-f195a39b513d49b2976aaf651de5cfcf |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T18:27:46Z |
| publishDate | 2009-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-f195a39b513d49b2976aaf651de5cfcf2022-12-22T03:21:12ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-12-0111121272128410.1593/neo.09494Human 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 MiceXiuying Chen0Lin Cheng1Xuemei Jia2Yi Zeng3Shuihong Yao4Zhigang Lv5Di Qin6Xin Fang7Yongliang Lei8Chun Lu9Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Youjiang Medical College for Nationalities, Bose 533000, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, PR ChinaLishui Center for Disease Control and Prevention, Lishui, Zhejiang, 323000, PR ChinaLaboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, PR ChinaKaposi 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, 3H-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.http://www.sciencedirect.com/science/article/pii/S1476558609800961 |
| spellingShingle | Xiuying Chen Lin Cheng Xuemei Jia Yi Zeng Shuihong Yao Zhigang Lv Di Qin Xin Fang Yongliang Lei Chun Lu 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 Neoplasia: An International Journal for Oncology Research |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558609800961 |
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