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K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation
Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosin...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478685/ https://www.ncbi.nlm.nih.gov/pubmed/31015491 http://dx.doi.org/10.1038/s41598-019-42763-0 |
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author | Tamanaha-Nakasone, Ayumi Uehara, Karina Tanabe, Yasuka Ishikawa, Haruna Yamakawa, Natsuko Toyoda, Zensei Kurima, Kiyoto Kina, Shinichiro Tsuneki, Masayuki Okubo, Yuko Yamaguchi, Sayaka Utsumi, Daisuke Takahashi, Kenzo Arakawa, Hirofumi Arasaki, Akira Kinjo, Takao |
author_facet | Tamanaha-Nakasone, Ayumi Uehara, Karina Tanabe, Yasuka Ishikawa, Haruna Yamakawa, Natsuko Toyoda, Zensei Kurima, Kiyoto Kina, Shinichiro Tsuneki, Masayuki Okubo, Yuko Yamaguchi, Sayaka Utsumi, Daisuke Takahashi, Kenzo Arakawa, Hirofumi Arasaki, Akira Kinjo, Takao |
author_sort | Tamanaha-Nakasone, Ayumi |
collection | PubMed |
description | Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer. |
format | Online Article Text |
id | pubmed-6478685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64786852019-05-03 K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation Tamanaha-Nakasone, Ayumi Uehara, Karina Tanabe, Yasuka Ishikawa, Haruna Yamakawa, Natsuko Toyoda, Zensei Kurima, Kiyoto Kina, Shinichiro Tsuneki, Masayuki Okubo, Yuko Yamaguchi, Sayaka Utsumi, Daisuke Takahashi, Kenzo Arakawa, Hirofumi Arasaki, Akira Kinjo, Takao Sci Rep Article Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer. Nature Publishing Group UK 2019-04-23 /pmc/articles/PMC6478685/ /pubmed/31015491 http://dx.doi.org/10.1038/s41598-019-42763-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tamanaha-Nakasone, Ayumi Uehara, Karina Tanabe, Yasuka Ishikawa, Haruna Yamakawa, Natsuko Toyoda, Zensei Kurima, Kiyoto Kina, Shinichiro Tsuneki, Masayuki Okubo, Yuko Yamaguchi, Sayaka Utsumi, Daisuke Takahashi, Kenzo Arakawa, Hirofumi Arasaki, Akira Kinjo, Takao K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title | K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title_full | K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title_fullStr | K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title_full_unstemmed | K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title_short | K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation |
title_sort | k1 gene transformation activities in aids-related and classic type kaposi’s sarcoma: correlation with clinical presentation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478685/ https://www.ncbi.nlm.nih.gov/pubmed/31015491 http://dx.doi.org/10.1038/s41598-019-42763-0 |
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