Genetic alterations disrupting the nuclear localization of the retinoblastoma-related gene RB2/p130 in human tumor cell lines and primary tumors.
作者： Gian Marco Tosi , Nadir Mario Maraldi , Luca Maria Neri , Caterina Cinti , Candace M. Howard
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摘要: The prototypic tumor suppressor gene, the retinoblastoma gene (RB/ p105), is mutated in a variety of human tumors. However, to date, mutational data on family members p107 and RB2/p130 tumors lacking. We studied expression pRb2/p130 by immunocytochemistry Western blot analysis panel osteosarcoma lymphoid cell lines. Only lines showed an abnormal cytoplasmic localization pRb2/p130, suggesting possible alterations within region nuclear signaling. screened these for genetic putative bipartite signal (NLS). This highly homologous with that RB/p105 gene. In addition, we four primary Burkitt's lymphomas Naturally occurring mutations, which disrupt NLS, were found lymphoma tumors, but not lines, where normal protein was detectable. Site-directed mutagenesis transfection assay using NLS mutants displayed markedly reduced biological activity as measured flow cytometric analysis. study clearly describes RB2/ p130 important target mutations subsequent inactivation pathogenesis, thus validating classical
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