Abstract
BackgroundOestrogen receptors (ER) have a well-established role to the initiation, progression and regulation of responses to treatment of breast, prostate, and lung cancers. Previous data indicates altered ER expression in oesophageal cancers (OC). However the role of ER subtypes and ER specific inhibitors in the regulation of OC progression remains unclear. This study sought to assess levels of ERα and ERβ in OC. The effects of highly selective ER antagonists on cell proliferation and apoptosis in two OC adenocarcinoma cell lines was also studied.MethodsERα and ERβ expression profiling in paired normal oesophageal mucosa and tumour tissues (n = 34; adenocarcinoma n = 28; squamous cell carcinoma n = 6) was performed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Correlation between levels of ER with the clinico-pathological features for OC was determined. The effect of selective ER antagonists on proliferation of OE33 and OE19 OC cell lines was studied.ResultsERα and ERβ mRNA expression was significantly higher (p < 0.05) in tumour tissues relative to their paired normal mucosa and correlated inversely with survival outcome (p < 0.05). Upregulation of ERα mRNA correlated with higher pathological T-stage (p < 0.05) and lymph node metastasis (p < 0.05) while ERβ mRNA upregulation correlated with positive vascular invasion (p < 0.05). A significant concentration-dependent inhibition of proliferation in OE33 and OE19 cell lines was induced by a highly-selective ERα antagonist (MPP) and an ERβ specific antagonist (PHTPP) (p < 0.05). Moreover, anti-oestrogens induced cell death through stimulation of apoptotic caspase activity.ConclusionThese findings indicate that the ER system is involved in OC progression and thus may provide a novel target for the treatment of OC.
Highlights
Oestrogen receptors (ER) have a well-established role to the initiation, progression and regulation of responses to treatment of breast, prostate, and lung cancers
These findings indicate that the ER system is involved in oesophageal cancers (OC) progression and may provide a novel target for the treatment of OC
Oestrogen receptor alpha (ERα) and Oestrogen receptor beta (ERβ) mRNAs are increased in oesophageal tumours To study the expression of ER in OC, primary tissues were collected from 34 OC patients (Table 1)
Summary
Oestrogen receptors (ER) have a well-established role to the initiation, progression and regulation of responses to treatment of breast, prostate, and lung cancers. It is evident that surgery alone is not a curative option for all stages of OC and additional adjunctive treatment modalities are needed [4, 5]. One of the characteristic features of OC, especially oesophageal adenocarcinoma (AC) is a persistence gender bias over several decades, in all races and across the world [6]. It occurs more frequently in males than in females, with a male to female ratio of 5–10:1, a fact that remains unexplained [7,8,9].
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