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MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851138/ https://www.ncbi.nlm.nih.gov/pubmed/24053468 http://dx.doi.org/10.1186/1471-230X-13-141 |
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author | Calcagno, Danielle Queiroz Freitas, Vanessa Morais Leal, Mariana Ferreira de Souza, Carolina Rosal Teixeira Demachki, Samia Montenegro, Raquel Assumpção, Paulo Pimentel Khayat, André Salim Smith, Marília de Arruda Cardoso dos Santos, Andrea Kely Campos Ribeiro Burbano, Rommel Rodriguez |
author_facet | Calcagno, Danielle Queiroz Freitas, Vanessa Morais Leal, Mariana Ferreira de Souza, Carolina Rosal Teixeira Demachki, Samia Montenegro, Raquel Assumpção, Paulo Pimentel Khayat, André Salim Smith, Marília de Arruda Cardoso dos Santos, Andrea Kely Campos Ribeiro Burbano, Rommel Rodriguez |
author_sort | Calcagno, Danielle Queiroz |
collection | PubMed |
description | BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer. |
format | Online Article Text |
id | pubmed-3851138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38511382013-12-06 MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer Calcagno, Danielle Queiroz Freitas, Vanessa Morais Leal, Mariana Ferreira de Souza, Carolina Rosal Teixeira Demachki, Samia Montenegro, Raquel Assumpção, Paulo Pimentel Khayat, André Salim Smith, Marília de Arruda Cardoso dos Santos, Andrea Kely Campos Ribeiro Burbano, Rommel Rodriguez BMC Gastroenterol Research Article BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer. BioMed Central 2013-09-23 /pmc/articles/PMC3851138/ /pubmed/24053468 http://dx.doi.org/10.1186/1471-230X-13-141 Text en Copyright © 2013 Calcagno 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 Article Calcagno, Danielle Queiroz Freitas, Vanessa Morais Leal, Mariana Ferreira de Souza, Carolina Rosal Teixeira Demachki, Samia Montenegro, Raquel Assumpção, Paulo Pimentel Khayat, André Salim Smith, Marília de Arruda Cardoso dos Santos, Andrea Kely Campos Ribeiro Burbano, Rommel Rodriguez MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title | MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title_full | MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title_fullStr | MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title_full_unstemmed | MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title_short | MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer |
title_sort | myc, fbxw7 and tp53 copy number variation and expression in gastric cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851138/ https://www.ncbi.nlm.nih.gov/pubmed/24053468 http://dx.doi.org/10.1186/1471-230X-13-141 |
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