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BMC Gastroenterology
Published in: BMC Gastroenterology 1/2013

Open Access 01-12-2013 | Research article

MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Authors: Danielle Queiroz Calcagno, Vanessa Morais Freitas, Mariana Ferreira Leal, Carolina Rosal Teixeira de Souza, Samia Demachki, Raquel Montenegro, Paulo Pimentel Assumpção, André Salim Khayat, Marília de Arruda Cardoso Smith, Andrea Kely Campos Ribeiro dos Santos, Rommel Rodriguez Burbano

Published in: BMC Gastroenterology | Issue 1/2013

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Abstract

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.
Appendix
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Metadata
Title
MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
Authors
Danielle Queiroz Calcagno
Vanessa Morais Freitas
Mariana Ferreira Leal
Carolina Rosal Teixeira de Souza
Samia Demachki
Raquel Montenegro
Paulo Pimentel Assumpção
André Salim Khayat
Marília de Arruda Cardoso Smith
Andrea Kely Campos Ribeiro dos Santos
Rommel Rodriguez Burbano
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2013
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-13-141

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