RESUMO
Transformed cells express high levels of non-telomeric reverse-transcriptase (RT) activity of retrotransposon and endogenous retrovirus origin. We previously reported that RT inhibition, either pharmacological or through transient silencing of RT-encoding LINE-1 (L1) elements by RNA interference (RNAi), reduced proliferation, induced differentiation and reprogrammed gene expression in human tumorigenic cell lines. Moreover, the antiretroviral drug efavirenz antagonized tumor progression in animal models in vivo. To get insight into the role of retroelements in tumorigenesis, we have now produced two cell lines derived from A-375 melanoma, in which the expression of either L1 retrotransposon, or HERV-K endogenous retrovirus, was stably suppressed by RNAi. Compared to the parental A-375 cell line, cells with stably interfered L1 expression show a lower proliferation rate, a differentiated morphology and lower tumorigenicity when inoculated in nude mice. L1 silencing modulates expression of several genes and, unexpectedly, also downregulates HERV-K expression. In HERV-K interfered cells, instead, L1 expression was unaffected, and cell proliferation and differentiation remained unchanged compared to parental A-375 cells. In vivo, however, their tumorigenic potential was found to be reduced after inoculation in nude mice. These results suggest that L1 and HERV-K play specific and distinct roles in cell transformation and tumor progression.
Assuntos
Diferenciação Celular , Proliferação de Células , Retrovirus Endógenos/genética , Elementos Nucleotídeos Longos e Dispersos/fisiologia , Melanoma Experimental/patologia , Retroelementos , Animais , Diferenciação Celular/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Progressão da Doença , Vetores Genéticos , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Melanoma Experimental/genética , Melanoma Experimental/prevenção & controle , Melanoma Experimental/virologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Retroelementos/genéticaRESUMO
Seventeen adolescents underwent arthroscopic lateral meniscectomy for discoid lateral meniscus. The average age at surgery was 13.6 years (range: 5-18 years). The main preoperative symptom was pain in 16 knees and extension loss in 1 knee. At arthroscopy, 10 menisci were complete, 4 were incomplete, and 3 were Wrisberg type. Arthroscopic total meniscectomy was performed in the 3 Wrisberg types, 2 complete types, and 1 incomplete type. The remaining menisci underwent partial meniscectomy. The average follow-up was 10 years (range: 5-15 years). According to the Ikeuchi rating system, 12 knees were rated as excellent (no symptoms and full range of motion), 4 were rated as good (occasional pain), and 1 was rated as fair (patellofemoral pain in an obese patient). Radiographic evaluation showed development of minor osteophytes in the lateral compartment of 8 knees and <50% narrowing of the lateral joint space in 11 knees. No correlation was found between meniscal type, type of meniscectomy (partial or total), and clinical and radiographic results. Arthroscopic lateral meniscectomy for discoid lateral meniscus in adolescents was effective in relieving symptoms during a 10-year follow-up period. Longer follow-up is needed to ascertain the significance of the radiographic changes seen in this study.