23 research outputs found
Histone H2A (H2A.X and H2A.Z) Variants in Molluscs: Molecular Characterization and Potential Implications For Chromatin Dynamics
Histone variants are used by the cell to build specialized nucleosomes, replacing canonical histones and generating functionally specialized chromatin domains. Among many other processes, the specialization imparted by histone H2A (H2A.X and H2A.Z) variants to the nucleosome core particle constitutes the earliest response to DNA damage in the cell. Consequently, chromatin-based genotoxicity tests have been developed in those cases where enough information pertaining chromatin structure and dynamics is available (i.e., human and mouse). However, detailed chromatin knowledge is almost absent in most organisms, specially protostome animals. Molluscs (which represent sentinel organisms for the study of pollution) are not an exception to this lack of knowledge. In the present work we first identified the existence of functionally differentiated histone H2A.X and H2A.Z variants in the mussel Mytilus galloprovincialis (MgH2A.X and MgH2A.Z), a marine organism widely used in biomonitoring programs. Our results support the functional specialization of these variants based on: a) their active expression in different tissues, as revealed by the isolation of native MgH2A.X and MgH2A.Z proteins in gonad and hepatopancreas; b) the evolutionary conservation of different residues encompassing functional relevance; and c) their ability to confer specialization to nucleosomes, as revealed by nucleosome reconstitution experiments using recombinant MgH2A.X and MgH2A.Z histones. Given the seminal role of these variants in maintaining genomic integrity and regulating gene expression, their preliminary characterization opens up new potential applications for the future development of chromatin-based genotoxicity tests in pollution biomonitoring programs
Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer
Acquisition of mitochondrial dysregulation and resistance to mitochondrial-mediated apoptosis after genotoxic insult in normal human fibroblasts: A possible model for early stage carcinogenesis
Differential expression of the multidrug resistance 1 (MDR1) protein in prostate cancer cells is independent from anticancer drug treatment and Y box binding protein 1 (YB-1) activity
Strong YB-1 Expression Predicts Liver Recurrence Following Resection for Colorectal Metastases
High Expression of Y-Box-Binding Protein-1 is Associated with Poor Survival in Resectable Esophageal Squamous Cell Carcinoma
p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines
PURPOSE: Multidrug resistance (MDR) is a major obstacle to the successful treatment of osteosarcoma with chemotherapy. Effectiveness of cancer therapy correlates with the ability to induce a p53-dependent apoptotic response. p53 is a tumor suppressor gene that is mutated in 22% of osteosarcomas. While impaired p53 has been implicated in the oncogenesis of osteosarcoma, it is unclear whether overexpression of wild type p53 can increase chemosensitivity in MDR osteosarcoma cells. METHODS: We transfected a plasmid encoding the wild type p53 gene to MDR osteosarcoma cell lines, which have different p53 statuses, U-2OSR2 with wild type p53 (Wt-p53) and KHOSR2 with mutant p53 (Mt-p53), and determined the effect of p53 overexpression on chemosensitivities. RESULTS: Both of the U-2OSR2 and KHOSR2 cell lines displayed similar trends in p53 induced drug sensitivities. However, it seems that the impact of p53 overexpression is different based on the differential intrinsic p53 status in these cell lines. In the KHOSR2 cell line (Mt-p53), overexpression of p53 up-regulates the expression of pro-apoptotic protein p21 and Bax, while in the U-2OSR2 cell line (Wt-p53), overexpression of p53 down-regulates IGF-1r expression significantly. CONCLUSIONS: These results demonstrated that tansfection of wild type p53 increases chemosensitivity through inhibiting either IGF-1r or through increasing the expression of pro-apoptotic proteins p21 and Bax in human MDR osteosarcoma cell lines