Jansson A, Gunnarsson C, Stål O
Department of Biomedicine and Surgery, Division of Oncology, Linköping University, S-581 85 Linköping, Sweden.
Endocr Relat Cancer. 2006 Sep;13(3):875-84. doi: 10.1677/erc.1.01181.
The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17beta-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.
绝经前女性雌激素的主要来源是卵巢，但绝经后，外周组织中的雌激素生物合成是唯一的生成部位。影响活性雌激素可用性的一组酶是17β-羟基类固醇脱氢酶（17HSD）家族。在乳腺癌中，主要研究了1型和2型17HSD，它们似乎是迄今为止涉及的主要17HSD酶。1型还是2型17HSD在乳腺肿瘤发展中最重要的问题仍不清楚。本研究的目的是研究在非肿瘤乳腺上皮细胞HMEC（人乳腺上皮细胞）和MCF10A中使用小干扰RNA（siRNA）使2型17HSD表达缺失，以及在乳腺癌衍生细胞系MCF7和T47D中使用瞬时转染使2型17HSD表达增加，如何影响以S期分数衡量的雌二醇转化和增殖率。我们进一步研究了这与所检测细胞系中1型17HSD和雌激素受体的内源性表达有何关系。在MCF7转染细胞和经siRNA处理的HMEC细胞中，培养基中的雌二醇水平发生了显著变化，但在T47D或MCF10A中未发生变化。在转染了2型17HSD的MCF7细胞和经siRNA处理的HMEC细胞中，S期分数降低。结果似乎取决于1型17HSD和雌激素受体的内源性表达。总之，我们发现2型17HSD的高表达或低表达均显著影响雌二醇浓度。然而，这种反应取决于1型17HSD的内源性表达。1型17HSD的表达似乎比2型17HSD更具主导性。因此，研究1型17HSD与2型17HSD之间的比例可能很重要。
