Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin.
Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators-Slug and E12/E47-in primary human gastric carcinomas and to compare this with the expression of E-cadherin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p<0.0001). Twenty-one cases (36%) showed E12/E47 up-regulation that was not significantly associated with E-cadherin down-regulation (p=0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p=0.0029) and with advanced pTNM stages (p=0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p=0.0014) and Snail in diffuse (p=0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators.
Alves
C Castro
CC
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Rua Dr Roberto Frias, S/N 4200-465 Porto, Portugal.
Rosivatz
E
E
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.|Division of Cell and Molecular Biology, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Schott
C
C
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.
Hollweck
R
R
Institut für Medizinische Statistik und Epidemiologie, Technische Universität München, Ismaningerstrasse 22, D-81675 Munich, Germany.
Becker
I
I
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.|Pathologie Rosenheim, Germany.
Sarbia
M
M
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.|Institut für Pathologie, Krankenhaus Lichtenberg, Berlin, Germany.
Carneiro
F
F
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Rua Dr Roberto Frias, S/N 4200-465 Porto, Portugal.|Faculdade de Medicina da Universidade do Porto and Hospital de S João, Alameda Hernâni Monteiro, 4200-319 Porto, Portugal.
Becker
K-F
KF
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81765 Munich, Germany.
D015820:Cadherins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004357:Drug Synergism; D004848:Epithelium / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics*; D051820:TCF Transcription Factors / Q000235:genetics; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
D015820:Cadherins; C108381:GEMIN2 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors