Oestrogen receptors in oesophageal cancer

Introduction: Oesophageal cancer is more common in men than women. Oestrogen, which mediates its effects via oestrogen receptors (ERs), may be responsible for the gender disparity. This thesis investigates the role of ERs in oesophageal cancer development and explores potential therapeutic possibilities. Methods: ERα and ERβ expression in oesophageal AC cell lines (OE19 and OE33) was knocked down using siRNA, and the effect of knockdown on the expression of proliferation-associated proteins (Ki67, PCNA, E-cadherin, Cyclin D) was assessed. The effect of the SERM, tamoxifen, on oesophageal cancer cell proliferation was investigated using proliferation assays and by evaluating the effect of tamoxifen on proliferation-associated proteins. Finally, a pilot study of tamoxifen in patients with oesophageal cancer was undertaken to assess feasibility of a clinical trial and to determine the short-term biological effect of tamoxifen on proliferation, assessed by a change in the immunohistochemical expression of Ki67 between paired biopsies. Results: ERα and ERβ are expressed at the mRNA (RT-PCR) and protein level (Western Blotting) in the OE19 and OE33 cell lines. ERβ mRNA knock down was achieved in the OE33 cell line (p=<0.0001). However, reproducible significant ERβ protein knockdown was not demonstrated, and there was no change in the expression of proliferation-associated proteins. Treatment with tamoxifen significantly inhibited OE33 cell proliferation in a dose-dependent manner (p=