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Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors
One of the resistance mechanisms to folate‐based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid cell line (W1L2) was made resistant to a lipophilic non‐polyglutamatable TS inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20‐fold i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1995
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920622/ https://www.ncbi.nlm.nih.gov/pubmed/8567390 http://dx.doi.org/10.1111/j.1349-7006.1995.tb03014.x |
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author | Kobayashi, Hiroyuki Takemura, Yuzuru Miyachi, Hayato Skelton, Lorraine Jackman, Ann L. |
author_facet | Kobayashi, Hiroyuki Takemura, Yuzuru Miyachi, Hayato Skelton, Lorraine Jackman, Ann L. |
author_sort | Kobayashi, Hiroyuki |
collection | PubMed |
description | One of the resistance mechanisms to folate‐based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid cell line (W1L2) was made resistant to a lipophilic non‐polyglutamatable TS inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20‐fold increase in TS enzyme activity with concomitant overexpression of TS mRNA. To overcome the resistance, we designed a ribozyme that can cleave the CUC sequences in a triple tandemly repeated sequence of TS mRNA. Expression of this ribozyme in W1L2:R179 cells transfected with Epstein Barr virus‐based expression vector resulted in sensitization to TS inhibitors concomitantly with a decrease of TS expression. The ribozyme expressed in transfectants was shown to be functional in cleaving artificial TS RNA in vitro. |
format | Online Article Text |
id | pubmed-5920622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59206222018-05-11 Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors Kobayashi, Hiroyuki Takemura, Yuzuru Miyachi, Hayato Skelton, Lorraine Jackman, Ann L. Jpn J Cancer Res Rapid Communication One of the resistance mechanisms to folate‐based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid cell line (W1L2) was made resistant to a lipophilic non‐polyglutamatable TS inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20‐fold increase in TS enzyme activity with concomitant overexpression of TS mRNA. To overcome the resistance, we designed a ribozyme that can cleave the CUC sequences in a triple tandemly repeated sequence of TS mRNA. Expression of this ribozyme in W1L2:R179 cells transfected with Epstein Barr virus‐based expression vector resulted in sensitization to TS inhibitors concomitantly with a decrease of TS expression. The ribozyme expressed in transfectants was shown to be functional in cleaving artificial TS RNA in vitro. Blackwell Publishing Ltd 1995-11 /pmc/articles/PMC5920622/ /pubmed/8567390 http://dx.doi.org/10.1111/j.1349-7006.1995.tb03014.x Text en |
spellingShingle | Rapid Communication Kobayashi, Hiroyuki Takemura, Yuzuru Miyachi, Hayato Skelton, Lorraine Jackman, Ann L. Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title | Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title_full | Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title_fullStr | Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title_full_unstemmed | Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title_short | Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors |
title_sort | effect of hammerhead ribozyme against human thymidylate synthase on the cytotoxicity of thymidylate synthase inhibitors |
topic | Rapid Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920622/ https://www.ncbi.nlm.nih.gov/pubmed/8567390 http://dx.doi.org/10.1111/j.1349-7006.1995.tb03014.x |
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