The role of estrogen receptor α and metastasis related gene 3 in human pancreatic cancer

Abstract

Objective To investigate the role of estrogen receptor α (ERα) and metastasis related gene 3 (MTA3) in epithelial-mesenchymal transition (EMT) via ERα→MTA3→Snail→E-cadherin signaling pathway and the correlation with cell apoptosis in pancreatic duct adenocarcinoma (PDAC) cells. Methods The expression of ERα MTA3 and EMT related factors Snail and E-cadherin in human PDAC tissues was detected by immunohistochemistry, and the results were further proved in human PDAC cell lines by Western blotting. Results Most of the ERα expression was detected in cytoplasm of PDAC cells. The expression of ERα had no correlation with tumor differentiation and patients’ gender. MTA3 was found in 50% of PDAC patients, Snail in 60% and E-cadherin in 80% respectively. More expression of MTA3 was found in patients without lymph node metastasis (PP: 1.39, IRS: 2.67 vs. PP: 0.81, IRS: 2.06). Snail in low-differentiated (PP: 1.61, IRS: 3.5) was found higher than low-moderate-differentiated (PP: 1.54, IRS: 2.69) and moderate-differentiated (PP: 1.40, IRS: 2.67) tissues. A significantly more expression of E-cadherin was found in better-differentiated PDAC tissues (P=0.026). The relationship of ERα→MTA3→Snail→E-cadherin signaling pathway was found in PDAC tissues, and MTA3 expression was correlated with less Snail and more E-cadherin. Further experiment in pancreatic cell lines had the same results as in human PDAC tissues. Conclusion The factors involved in ERα→MTA3→Snail→E-cadherin signaling pathway existed in pancreatic cancer tissues, and this pathway existed in a subgroup of PDAC tissues. MTA3 is an upper stream regulator of EMT, and correlated with differentiation of PADC cells. Key words: Pancreatic adenocarcinoma; Estrogen receptor α; Metastasis related gene 3; Epithelial-mesenchymal transition