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Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant

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...

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Autores principales: Ottey, M, Han, S-Y, Druck, T, Barnoski, B L, McCorkell, K A, Croce, C M, Raventos-Suarez, C, Fairchild, C R, Wang, Y, Huebner, K
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410021/
https://www.ncbi.nlm.nih.gov/pubmed/15494723
http://dx.doi.org/10.1038/sj.bjc.6602058
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author Ottey, M
Han, S-Y
Druck, T
Barnoski, B L
McCorkell, K A
Croce, C M
Raventos-Suarez, C
Fairchild, C R
Wang, Y
Huebner, K
author_facet Ottey, M
Han, S-Y
Druck, T
Barnoski, B L
McCorkell, K A
Croce, C M
Raventos-Suarez, C
Fairchild, C R
Wang, Y
Huebner, K
author_sort Ottey, M
collection PubMed
description 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; ∼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 ∼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 exhibit >5-fold increased mutation frequency. This increased mutation burden could explain the susceptibility of Fhit-deficient cells in vivo to malignant transformation.
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spelling pubmed-24100212009-09-10 Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant Ottey, M Han, S-Y Druck, T Barnoski, B L McCorkell, K A Croce, C M Raventos-Suarez, C Fairchild, C R Wang, Y Huebner, K Br J Cancer Molecular and Cellular Pathology 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; ∼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 ∼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 exhibit >5-fold increased mutation frequency. This increased mutation burden could explain the susceptibility of Fhit-deficient cells in vivo to malignant transformation. Nature Publishing Group 2004-11-01 2004-10-19 /pmc/articles/PMC2410021/ /pubmed/15494723 http://dx.doi.org/10.1038/sj.bjc.6602058 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular and Cellular Pathology
Ottey, M
Han, S-Y
Druck, T
Barnoski, B L
McCorkell, K A
Croce, C M
Raventos-Suarez, C
Fairchild, C R
Wang, Y
Huebner, K
Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title_full Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title_fullStr Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title_full_unstemmed Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title_short Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant
title_sort fhit-deficient normal and cancer cells are mitomycin c and uvc resistant
topic Molecular and Cellular Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410021/
https://www.ncbi.nlm.nih.gov/pubmed/15494723
http://dx.doi.org/10.1038/sj.bjc.6602058
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