Abstract
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.
Highlights
Kaposi’s sarcoma (KS) is an intermediate malignant soft tissue tumor that primarily affects cutaneous tissue; it may spread to the lymph nodes and visceral organs
Primary mouse embryonic fibroblasts (MEFs), CF-1 line, were infected with AIDS-related K1 or classic K1 gene, AK1 and CF-1classic K1 (CK1), respectively, and transformation activity of K1 was assessed by comparing cellular proliferation between AK1 and CK1 cells
These results showed that the proliferation activity of AIDS-related K1 is higher than that of classic K1
Summary
Kaposi’s sarcoma (KS) is an intermediate malignant soft tissue tumor that primarily affects cutaneous tissue; it may spread to the lymph nodes and visceral organs. We compared the K1 gene sequence between AIDS-related KS and classic KS in Okinawa, where a considerable number of classic KS cases have been reported[17]. The K1 amino acid sequence of classic KS in Okinawa showed a five amino acid deletion in variable region 2 (VR2), and many amino acid substitutions in both VR1 and VR2 when compared with those of AIDS-related KS17. These results implicate that the transformation activity of K1 between AIDS-related KS and classic KS is different, and the difference may be associated with clinical presentation. This is the first report comparing the transformation activity of the K1 gene between AIDS-related KS and classic KS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
