1. The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma
- Author
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Paul Downey, Baoqiang Guo, Andrew D. Sharrocks, Christian Gulmann, Yeng Ang, and Richard Keld
- Subjects
MAPK/ERK pathway ,Cancer Research ,Subfamily ,Esophageal Neoplasms ,Blotting, Western ,Context (language use) ,Biology ,Adenocarcinoma ,In Vitro Techniques ,lcsh:RC254-282 ,ETV1 ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Humans ,Extracellular Signal-Regulated MAP Kinases ,Transcription factor ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Proto-Oncogene Proteins c-ets ,Cell growth ,Reverse Transcriptase Polymerase Chain Reaction ,Research ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Immunohistochemistry ,body regions ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Adenovirus E1A Proteins ,Matrix Metalloproteinase 1 ,Transcription Factors - Abstract
Background Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Results Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. Conclusions This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.
- Published
- 2010