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TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status

BACKGROUND: Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs c...

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Autores principales: Herreros-Villanueva, Marta, Muñiz, Pilar, García-Girón, Carlos, Cavia-Saiz, Mónica, del Corral, María J Coma
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841128/
https://www.ncbi.nlm.nih.gov/pubmed/20146801
http://dx.doi.org/10.1186/1479-5876-8-15
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author Herreros-Villanueva, Marta
Muñiz, Pilar
García-Girón, Carlos
Cavia-Saiz, Mónica
del Corral, María J Coma
author_facet Herreros-Villanueva, Marta
Muñiz, Pilar
García-Girón, Carlos
Cavia-Saiz, Mónica
del Corral, María J Coma
author_sort Herreros-Villanueva, Marta
collection PubMed
description BACKGROUND: Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer. The purpose of this study was to evaluate the impact of TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different K-Ras and B-Raf mutational status. METHODS: TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2. mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting and cell viability was analyzed by the MTT method. RESULTS: We found that mRNA and TAp73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when B-Raf is mutated. This was statistically significant and was also associated with higher cell viability after the treatment. CONCLUSIONS: Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function. Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab.
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spelling pubmed-28411282010-03-18 TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status Herreros-Villanueva, Marta Muñiz, Pilar García-Girón, Carlos Cavia-Saiz, Mónica del Corral, María J Coma J Transl Med Research BACKGROUND: Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer. The purpose of this study was to evaluate the impact of TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different K-Ras and B-Raf mutational status. METHODS: TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2. mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting and cell viability was analyzed by the MTT method. RESULTS: We found that mRNA and TAp73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when B-Raf is mutated. This was statistically significant and was also associated with higher cell viability after the treatment. CONCLUSIONS: Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function. Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab. BioMed Central 2010-02-10 /pmc/articles/PMC2841128/ /pubmed/20146801 http://dx.doi.org/10.1186/1479-5876-8-15 Text en Copyright ©2010 Herreros-Villanueva et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Herreros-Villanueva, Marta
Muñiz, Pilar
García-Girón, Carlos
Cavia-Saiz, Mónica
del Corral, María J Coma
TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title_full TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title_fullStr TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title_full_unstemmed TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title_short TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status
title_sort tap73 is one of the genes responsible for the lack of response to chemotherapy depending on b-raf mutational status
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841128/
https://www.ncbi.nlm.nih.gov/pubmed/20146801
http://dx.doi.org/10.1186/1479-5876-8-15
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