RESUMO
Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.
Assuntos
Doenças do Cão/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Meníngeas/veterinária , Meningioma/veterinária , Neurofibromatose 2/metabolismo , Neurofibromina 2/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting/veterinária , Doenças do Cão/genética , Doenças do Cão/metabolismo , Cães , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Neurofibromatose 2/genética , Neurofibromina 2/genética , RNA Neoplásico/química , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Proteínas Supressoras de Tumor/genéticaRESUMO
Tumor suppressor in lung cancer-1 (TSLC1) loss is common in many human cancers, including meningioma. In this study, we demonstrate that TSLC1 protein and RNA expression is lost in 60% to 65% of high-grade gliomas, and that TSLC1 reintroduction into glioma cells results in growth suppression. Moreover, Tslc1 loss in mice results in increased astrocyte proliferation in vivo and in vitro. These data indicate that TSLC1 functions as a glioma tumor suppressor.
