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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

Selective oestrogen receptor antagonists inhibit oesophageal cancer cell proliferation in vitro

Zeitschrift:
BMC Cancer > Ausgabe 1/2018
Autoren:
Waleed Al-Khyatt, Cristina Tufarelli, Raheela Khan, Syed Yousef Iftikhar
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12885-018-4030-5) contains supplementary material, which is available to authorized users.

Abstract

Background

Oestrogen 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.

Methods

ERα 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.

Results

ERα 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.

Conclusion

These findings indicate that the ER system is involved in OC progression and thus may provide a novel target for the treatment of OC.
Zusatzmaterial
Additional file 1: Figure S1. Identification of suitable reference genes. Reference genes expression stability was analysed using geNorm and NormFinder. Figure S2. E2 treatment does not alter proliferation of OE33 and OE19 cells. Bar chart demonstrates the effect of increasing dose of E2 on OE33 and OE19 cell lines proliferation. (PDF 348 kb)
12885_2018_4030_MOESM1_ESM.pdf
Literatur
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