K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation

Autor: Natsuko Yamakawa, Kiyoto Kurima, Akira Arasaki, Zensei Toyoda, Yasuka Tanabe, Shinichiro Kina, Hirofumi Arakawa, Kenzo Takahashi, Takao Kinjo, Haruna Ishikawa, Sayaka Yamaguchi, Masayuki Tsuneki, Daisuke Utsumi, Yuko Okubo, Karina Uehara, Ayumi Tamanaha-Nakasone
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Skin Neoplasms
Remission
Spontaneous
lcsh:Medicine
Ataxia Telangiectasia Mutated Proteins
Biology
medicine.disease_cause
Severity of Illness Index
Cell Line
Mice
Viral Proteins
03 medical and health sciences
Transformation
Genetic
0302 clinical medicine
Downregulation and upregulation
medicine
Animals
Humans
RNA
Small Interfering
lcsh:Science
Sarcoma
Kaposi
Gene
Kaposi's sarcoma
Protein kinase B
Regulation of gene expression
Multidisciplinary
AIDS-Related Opportunistic Infections
lcsh:R
NF-kappa B
Fibroblasts
medicine.disease
Gene Expression Regulation
Neoplastic
Transformation (genetics)
Cell Transformation
Neoplastic
030104 developmental biology
Checkpoint Kinase 1
Herpesvirus 8
Human
Host-Pathogen Interactions
Cancer research
lcsh:Q
Signal transduction
Carcinogenesis
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
HeLa Cells
Signal Transduction
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
ISSN: 2045-2322
DOI: 10.1038/s41598-019-42763-0
Popis: 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.
Databáze: OpenAIRE
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