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X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts
Ataxia‐telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradi‐ated and X‐irradiated EBV (Epstein‐Barr virus)‐transformed lymphoblastoid cell lines (LCLs) derived from dono...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926759/ https://www.ncbi.nlm.nih.gov/pubmed/11429062 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01152.x |
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author | Hirai, Yuko Hayashi, Tomonori Kubo, Yoshiko Hoki, Yuko Arita, Izumi Tatsumi, Kouichi Seyama, Toshio |
author_facet | Hirai, Yuko Hayashi, Tomonori Kubo, Yoshiko Hoki, Yuko Arita, Izumi Tatsumi, Kouichi Seyama, Toshio |
author_sort | Hirai, Yuko |
collection | PubMed |
description | Ataxia‐telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradi‐ated and X‐irradiated EBV (Epstein‐Barr virus)‐transformed lymphoblastoid cell lines (LCLs) derived from donors who were normal (ATM+/+), AT heterozygotes (ATM+/−), or AT homozy‐gotes (ATM−/−), respectively. In ATM+/+ LCLs, the levels of ATM mRNA were found to have increased by approximately 1.5‐fold within 1 h of exposure to 10 Gy of X‐rays, while the ATM protein levels had increased by 1.5‐ to 2.0‐fold within 2 to 3 h of irradiation. The wild‐type mRNA and protein levels both returned to their basal values fairly quickly after this tune. The results obtained with the ATM+/− LCLs were quite different, however: neither the mRNA nor protein levels were found to have increased as a consequence of X‐irradiation in any ATM+/− LCL. Twelve of the mutations in the ATM−/− LCLs we used were truncating mutations, and we suspected that the corresponding truncated ATM proteins would be too labile to be detected by western blot analysis. However, five of the ATM−/− LCLs produced mutant ATM proteins that were identical in molecular weight to the wild‐type ATM protein. When cells from three of these five clones were exposed to X‐rays, transcription of the mutant ATM genes appeared to reduce somewhat, as were the levels of protein being produced. These results suggest that the normal ATM gene responds to ionizing radiation by up‐regulating its activity, whereas none of the mutant ATM genes we studied were able to respond in this way. |
format | Online Article Text |
id | pubmed-5926759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59267592018-05-11 X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts Hirai, Yuko Hayashi, Tomonori Kubo, Yoshiko Hoki, Yuko Arita, Izumi Tatsumi, Kouichi Seyama, Toshio Jpn J Cancer Res Article Ataxia‐telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradi‐ated and X‐irradiated EBV (Epstein‐Barr virus)‐transformed lymphoblastoid cell lines (LCLs) derived from donors who were normal (ATM+/+), AT heterozygotes (ATM+/−), or AT homozy‐gotes (ATM−/−), respectively. In ATM+/+ LCLs, the levels of ATM mRNA were found to have increased by approximately 1.5‐fold within 1 h of exposure to 10 Gy of X‐rays, while the ATM protein levels had increased by 1.5‐ to 2.0‐fold within 2 to 3 h of irradiation. The wild‐type mRNA and protein levels both returned to their basal values fairly quickly after this tune. The results obtained with the ATM+/− LCLs were quite different, however: neither the mRNA nor protein levels were found to have increased as a consequence of X‐irradiation in any ATM+/− LCL. Twelve of the mutations in the ATM−/− LCLs we used were truncating mutations, and we suspected that the corresponding truncated ATM proteins would be too labile to be detected by western blot analysis. However, five of the ATM−/− LCLs produced mutant ATM proteins that were identical in molecular weight to the wild‐type ATM protein. When cells from three of these five clones were exposed to X‐rays, transcription of the mutant ATM genes appeared to reduce somewhat, as were the levels of protein being produced. These results suggest that the normal ATM gene responds to ionizing radiation by up‐regulating its activity, whereas none of the mutant ATM genes we studied were able to respond in this way. Blackwell Publishing Ltd 2001-06 /pmc/articles/PMC5926759/ /pubmed/11429062 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01152.x Text en |
spellingShingle | Article Hirai, Yuko Hayashi, Tomonori Kubo, Yoshiko Hoki, Yuko Arita, Izumi Tatsumi, Kouichi Seyama, Toshio X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title | X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title_full | X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title_fullStr | X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title_full_unstemmed | X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title_short | X‐Irradiation Induces Up‐regulation of ATM Gene Expression in Wild‐type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia‐telangiectasia Counterparts |
title_sort | x‐irradiation induces up‐regulation of atm gene expression in wild‐type lymphoblastoid cell lines, but not in their heterozygous or homozygous ataxia‐telangiectasia counterparts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926759/ https://www.ncbi.nlm.nih.gov/pubmed/11429062 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01152.x |
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