In vitro study of the effects of estrogen receptor beta expression on the biological behavior of a human breast cancer cell line
Hou, Y-feng.; Yuan, S-tao.; Li, H-cheng.; Wu, J.; Lu, J-song.; Lu, L-juan.; Liu, G.; Shen, Z-zhou.; Ding, J.; Shao, Z-min.
Zhonghua Zhong Liu Za Zhi 27(7): 389-392
2005
ISSN/ISBN: 0253-3766 PMID: 16188119 Document Number: 585543
Objective To study effects of estrogen receptor beta (ER beta) on the biological behavior of a human breast cancer cell line MDA-MB-435. Methods Human ER beta cDNA was introduced into MDA-MB-435 cells by stable transfection. Effects of ER (3 expression on cell proliferation and invasion were investigated by NIT, flow cytometry and transwell techniques. Cyclin A, cyclin E, cyclin D1, p21, WIN, Ets-1, VEGF and b-FGF were detected by RT-PCR and/or Western blot or gelatin zymography. Results ER beta was shown to be able to significantly increase the proliferation and invasion of MDA-MB-435 cells in an estradiol-independent manner. The S phase distribution of the cells with ER (3 overexpression was 46.8%, significantly higher than that of wild type (29.9%) and mock transfected cells (27.6%) ( P = 0.01). In ER beta transfected cells, the expression of p21 decreased by 33.3% at mRNA level (P = 0.03) and by 47.4% at protein level (P = 0.02), respectively. The expression of MMP-9 increased by 91.3% at mRNA level (P < 0.01) and its activity was up-regulated by 67.3% (P = 0.02). Furthermore, the mRNA and protein levels of Ets-1 increased 62.2% ( P = 0.01) and 51.0% ( P = 0.01), respectively. No significant difference was observed in the mRNA levels of cyclin A, cyclin E, cyclin D1, MMP-1, MMP-2, MMP-7, VEGF and b-FGF among these cells. Conclusion ER beta can enhance proliferation and invasion of breast cancer cells. Down-regulation of p21 and up-regulation of MMP-9 and Ets-1 may be involved in its mechanisms.