RT Journal Article
SR Electronic
T1 CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1115
OP 1123
DO 10.1136/gutjnl-2011-300427
VO 61
IS 8
A1 Joana Caldeira
A1 Joana Simões-Correia
A1 Joana Paredes
A1 Marta T Pinto
A1 Sónia Sousa
A1 Giovanni Corso
A1 Daniele Marrelli
A1 Franco Roviello
A1 Paulo S Pereira
A1 Dominique Weil
A1 Carla Oliveira
A1 Fernando Casares
A1 Raquel Seruca
YR 2012
UL http://gut.bmj.com/content/61/8/1115.abstract
AB Background Gastric cancer (GC) is a highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer-associated deaths worldwide. Although many genes have been implicated in its development, many cases remain genetically unexplained. Hence, there is an urgent need to find new disease-related genes.Methods A transgenic Drosophila model was used to screen for novel genes putatively involved in GC. The authors evaluated the expression of the most interesting candidates in GC cell lines and primary tumours by semi-quantitative reverse transcription PCR, dissected the molecular mechanisms responsible for the deregulation of the most relevant one, and analysed its functional role in vitro and in a chicken embryo model.Results Six candidate genes were identified, of which cytoplasmic polyadenylation element binding protein 1 (CPEB1) was downregulated in all GC cell lines and in 11 of 12 primary GC tumours. The pivotal CPEB1 promoter CpG site was determined, and it was found that methylation at this 79th CpG site was associated with CPEB1 silencing in GC cell lines and primary tumours. It was also discovered that methylation of this site was significantly more prevalent in diffuse type GC (p=0.007) and in cases with lymph node metastases (p=0.042). In vitro, CPEB1 impaired invasion. Its antiangiogenic role was also discovered, which was associated with downregulation of MMP14 and VEGFA.Conclusions The first evidence of CPEB1 involvement in GC is presented, along with the molecular mechanism underlying the regulation of its expression and its potential role in invasion and angiogenesis.