2024-03-29T14:33:29Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02012586
2022-10-31T07:05:33Z
1642838158423:1642838158860:1642838159351
1642838403551:1642838409905
K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma : Correlation with clinical presentation
Uehara, Karina
上原, 佳里奈
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.
学位論文
博士(医学)
http://purl.org/coar/resource_type/c_db06
琉球大学
University of the Ryukyus
2020-04-23
2020-03-24
VoR
http://hdl.handle.net/20.500.12000/46707
2045-2322
scientific reports
6416
9
甲第505号
eng
https://doi.org/10.1038/s41598-019-42763-0
https://doi.org/10.1038/s41598-019-42763-0
open access
© The Author(s) 2019
http://creativecommons.org/licenses/by/4.0/