TY - JOUR
T1 - Activation of epidermal growth factor receptor results in Snail protein but not mRNA overexpression in endometrial cancer
AU - Hipp, Susanne
AU - Walch, Axel
AU - Schuster, Tibor
AU - Losko, Sascha
AU - Laux, Holger
AU - Bolton, T.
AU - Höfler, Heinz
AU - Becker, Karl Friedrich
PY - 2009/9
Y1 - 2009/9
N2 - 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-3β 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.
AB - 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-3β 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.
KW - E-cadherin
KW - EGFR
KW - Endometrial carcinoma
KW - Her2
KW - Protein microarray
KW - Snail
UR - http://www.scopus.com/inward/record.url?scp=77449112393&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2008.00526.x
DO - 10.1111/j.1582-4934.2008.00526.x
M3 - Article
C2 - 19604315
AN - SCOPUS:77449112393
SN - 1582-1838
VL - 13
SP - 3858
EP - 3867
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 9 B
ER -