Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
| Autor: | Fairchild Cr, Kelly A. McCorkell, Ya Wang, B.L. Barnoski, Carlo M. Croce, Kay Huebner, Shuang-Yin Han, Raventos-Suarez C, Teresa Druck, Michelle Ottey |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Cell Apoptosis Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Kidney Radiation Tolerance Malignant transformation Mice 0302 clinical medicine Fhit protein FHIT Tumor Cells Cultured Genes Tumor Suppressor Mutation frequency 0303 health sciences Cell Cycle Cell cycle Acid Anhydride Hydrolases Neoplasm Proteins 3. Good health Gene Expression Regulation Neoplastic Cell Transformation Neoplastic medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Signal Transduction Ultraviolet Rays Mitomycin UVC resistance Fhit deficiency Protein Serine-Threonine Kinases Biology DNA damage checkpoint Colony-Forming Units Assay 03 medical and health sciences Stomach Neoplasms medicine Animals Humans neoplasms 030304 developmental biology Mitomycin C Molecular and Cellular Pathology DNA Kinetics Drug Resistance Neoplasm Checkpoint Kinase 1 Mutation Cancer cell Cancer research mitomycin C resistance Protein Kinases |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6602058 |
| Popis: | To identify functions of the fragile tumour suppressor gene, FHIT, matched pairs of Fhit-negative and -positive human cancer cell clones, and normal cell lines established from Fhit -/- and +/+ mice, were stressed and examined for differences in cell cycle kinetics and survival. A larger fraction of Fhit-negative human cancer cells and murine kidney cells survived treatment with mitomycin C or UVC light compared to matched Fhit-positive cells; approximately 10-fold more colonies of Fhit-deficient cells survived high UVC doses in clonigenic assays. The human cancer cells were synchronised in G1, released into S and treated with UVC or mitomycin C. At 18 h post mitomycin C treatment approximately 6-fold more Fhit-positive than -negative cells had died, and 18 h post UVC treatment 3.5-fold more Fhit-positive cells were dead. Similar results were obtained for the murine -/- cells. After low UVC doses, the rate of DNA synthesis in -/- cells decreased more rapidly and steeply than in +/+ cells, although the Atr-Chk1 pathway appeared intact in both cell types. UVC surviving Fhit -/- cells appear transformed and exhibit5-fold increased mutation frequency. This increased mutation burden could explain the susceptibility of Fhit-deficient cells in vivo to malignant transformation. |
| Databáze: | OpenAIRE |
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