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The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma
- Source :
- Molecular Cancer, Molecular Cancer, Vol 9, Iss 1, p 313 (2010)
- Publication Year :
- 2010
-
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.
- 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
Subjects
Details
- ISSN :
- 14764598
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular cancer
- Accession number :
- edsair.doi.dedup.....de5920d14cb2a337a2bb2ec76adbbbc9