title: Activation of epidermal growth factor receptor results in snail protein but not mRNA overexpression in endometrial cancer.
abstract: Reduced E-cadherin expression is associated with tumour progression of many carcinomas, including endometrial cancers. The transcription factor Snail is known as one of the most prominent transcriptional E-cadherin repressors; its regulation in cancer tissues, however, still remains unclear. Here, we report that activation of epidermal growth factor receptor (EGFR) resulted in overexpression of Snail and also identified critical downstream signalling molecules. Stimulation of two endometrial carcinoma cell lines with epidermal growth factor (EGF) lead to an increase of Snail protein expression. In primary human endometrioid endometrial carcinomas Snail protein expression correlated with the activated, phosphorylated form of EGFR (Tyr1086) as revealed by profiling 24 different signalling proteins using protein lysate microarrays. In addition, we observed an inverse correlation between Snail and E-cadherin protein levels in these tumours. Most likely, p38 MAPK, PAK1, AKT, ERK1/2 and GSK-3beta are involved in the up-regulation of Snail downstream of EGFR. Snail mRNA expression did not show a correlation with activated EGFR in these tumours. Taken together, profiling of signalling proteins in primary human tissues provided strong evidence that EGFR signalling is involved in Snail protein overexpression.
authors: Technische Universitaet Muenchen, Institut fuer Pathologie, Muenchen, Germany.
authors: Susanne
authors: S
authors: Hipp
authors: Axel
authors: A
authors: Walch
authors: Tibor
authors: T
authors: Schuster
authors: Sascha
authors: S
authors: Losko
authors: Holger
authors: H
authors: Laux
authors: T
authors: T
authors: Bolton
authors: Heinz
authors: H
authors: Höfler
authors: Karl-Friedrich
authors: KF
authors: Becker
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors