Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: Comparison of four oestrogens. (February 2015)

• Record Type: Journal Article
• Authors: Liu, Shunyu; Ruan, Xiangyan; Schultz, Silke; Neubauer, Hans; Fehm, Tanja; Seeger, Harald; Mueck, Alfred O.
• Is Part Of: European journal of contraception & reproductive health care. Volume 20:Number 1(2015:Feb.)
• Page Start: 29
• Page End: 35
• Publication Date: 2015-02
• Subjects: Breast cancer -- Contraception -- Estetrol -- Hormone replacement therapy -- Oestetrol; Contraception -- Periodicals; Reproductive health -- Periodicals; Generative organs, Female -- Periodicals; Contraception -- Periodicals; Reproductive Medicine -- Periodicals; 613.9
• DOI: 10.3109/13625187.2014.951997
• Languages: English
• ISSNs: 1362-5187

Abstract

Abstract: Objectives Oestetrol (15-alpha-hydroxyoestriol, E4 ) is an endogenous oestradiol metabolite mainly produced at high concentrations in the fetal liver. In earlier studies E4 was investigated for its use as marker for pregnancies at risk, especially with vascular problems. Some current investigations suggest that the use of E4 in hormone therapy or contraception may have advantages in terms of breast cancer risk when compared to other oestrogens. Methods Proliferation of two oestrogen receptor-positive breast cancer cell lines (ZR 75-1 and HCC 1500) was investigated after incubation with oestrone (E1 ), oestradiol (E2 ), oestriol (E3 ), and oestetrol (E4 ). Receptor expression of oestrogen receptor-alpha (ERα) and -beta (ERβ) was determined by Western-Blot. Results All four oestrogens elicited a significant proliferative stimulation at concentrations of 10 −10 und 10 −9 M as compared to controls. Oestrone displayed a significantly weaker effect than E2 . Oestetrol was significantly less effective than E2 at the lower concentration. Expression of ERα and ERβ was significantly upregulated by all oestrogens tested, without differences between the latter. Conclusions Our results indicate a slightly lower proliferative effect of E4, but only at low concentrations. However, no difference was found regarding receptor expression. Breast cancer risk associated with use of oestetrol should be tested in clinical trials. Chinese Abstract 摘要 雌四醇(15α-羟雌三醇，E4 )是一种内源性雌二醇代谢物，主要在胎儿肝脏产生高浓度的雌四醇。早期研究了E4 作为妊娠风险标记物的应用, 尤其在血管问题。目前一些研究表明，激素治疗或避孕药中应用E4 ，与其它的雌激素相比，可能在乳腺癌风险方面有优势。我们研究了雌酮(E1 ), 雌二醇(E2 )、雌三醇(E3 )和雌四醇(E4 )对雌激素受体阳性的两种乳腺癌细胞(ZR75-1 和 HCC1500)的增殖影响。蛋白质印迹法检测雌激素受体ERα和ERβ的表达。与对照组比较，四种雌激素在10 ﹣10 和 10 ﹣9 M浓度下，均引起明显的增殖反应。与E2 比较，雌酮显示明显低增殖反应。低浓度雌四醇与E2 比较，显示明显低增殖反应。所有雌激素显著上调ERα和ERβ的表达，后者没有差别。研究结果显示，只在较低浓度下，E4 显示略低的增殖反应，而受体表达无差异。乳腺癌风险与雌四醇应用的相关性应进行临床试验。