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Female sex hormonal effects on clusterin expression in endometrial and breast adenocarcinoma cell lines
Dong Choon Park1, Min Jung Suh1, Seung Geun Yeo2
1St Vincents' Hospital, The Catholic University of Korea, Korea; 2East-West Medical Research Institute, Kyung Hee University, Korea
Clusterin is a heterodimeric glycoprotein that is synthesised in a wide variety of tissues. We have investigated the regulation of clusterin expression under the female sex hormones in endometrial and breast adenocarcinoma cell lines. And we compared clusterin expression according to the hormone levels and the paclitaxel resistance.
The expression levels of clusterin in endometrial adenocarcinoma cell lines (KLE, ECC) and breast adenocarcinoma cell lines (MDAMB, BT474, T47D) were validated by performing western blotting. And the correlation between clusterin expression levels and the IC50 of paclitaxel was tested. After transfection of clusterin siRNA on KLE, T47D, which expressed high level of clusterin we evaluated their effect on paclitaxel-sensitivity by XTT assay. And also we evaluated the paclitaxel-sensitivity under the female sex hormones (Estradiol, Follicular stimulating Hormone, Progesterone).
Among the female sex hormones, the effect of Estradiol and Follicular stimulating hormone are significantly pronounced clusterin expression in both endometrial and breast adenocarcinoma cell lines whatever they have hormonal receptor or not. In case of progesterone, breast adenocarcinoma cell lines are in marked contrast to expression of clusterin but endometrial adenocarcinoma cell lines are decreased the expression of clusterin. In both cases the expression level of clusterin is correlated with pacltiaxel resistance (P< 0.001).
These data suggest that clusterin expression is tightly regulated by oestrogen and Follicular stimulating Hormone in endometrial and breast adenocarcinoma cell lines. There may be a complex mechanism of regulation of clusterin expression in the normal and cancerous endometrium.
