Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan.
Taiwan J Obstet Gynecol. 2013 Sep;52(3):365-73. doi: 10.1016/j.tjog.2012.09.038.
To examine the effects of 17β-estradiol (E2) and progestogens, used in hormone therapy, on estrogen receptors (ER), progesterone receptors (PR), and human breast tumor cell growth.
MCF-7 cells were incubated in pure E2 (1 nM and 10 nM) as well as in E2 in conjunction with 10 nM progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NET), and cyproterone acetate (CPA). Cell proliferation, apoptosis, expression of caspase-3, and both ER and PR isoforms were evaluated.
Caspase-3 was significantly diminished in cultures with only E2, whereas ERα significantly increased. A significant increase of caspase-3 in addition to the entire abolishment of E2-induced augmentation of ERα was observed in 1 nM E2 plus MPA and 10 nM E2 plus NET, whereas PR isoform B (PRB) was significantly increased. The ratios of apoptosis: proliferation significantly increased in 1 nM E2 plus progestogens (except P4) and 10 nM E2 plus NET. The changes of the PRA/PRB ratio were inversely related to the changes of the apoptosis to proliferation ratio. Significant increase of ERβ and PRB was noted in the E2 plus MPA or NET, in addition to a significant increase of ERα and decrease of PRA in the E2 plus CPA, as well as an increase of ERα and decrease of PRA and PRB in the E2 plus P4.
The combination of E2 and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.
研究雌激素（E2）和孕激素在激素治疗中的作用对雌激素受体（ER）、孕激素受体（PR）和人乳腺癌细胞生长的影响。
MCF-7 细胞分别用纯 E2（1 nM 和 10 nM）及 E2 联合 10 nM 孕激素（包括孕酮（P4）、醋酸甲羟孕酮（MPA）、左炔诺孕酮（NET）和醋酸环丙孕酮（CPA））孵育。检测细胞增殖、凋亡、半胱天冬酶-3 的表达以及 ER 和 PR 同工型。
仅用 E2 培养时，半胱天冬酶-3 的表达显著减少，而 ERα 则显著增加。在 1 nM E2 加 MPA 和 10 nM E2 加 NET 中，除了观察到 E2 诱导的 ERα 增加完全消除外，还观察到 caspase-3 显著增加，同时 PR 同工型 B（PRB）显著增加。在 1 nM E2 加孕激素（除 P4 外）和 10 nM E2 加 NET 中，凋亡：增殖的比值显著增加。PRA/PRB 比值的变化与凋亡与增殖比值的变化呈反比。在 E2 加 MPA 或 NET 中，除了 ERβ 和 PRB 的显著增加外，还观察到 ERα 的显著增加和 PRA 的减少，在 E2 加 CPA 中，除了 ERα 的增加和 PRA 和 PRB 的减少外，还观察到 ERα 的增加和 PRA 和 PRB 的减少。
E2 与各种孕激素的联合使用对 ER 和 PR 的表达产生了不同的影响，从而对 MCF-7 细胞的生长产生了不同的影响。与 P4 相比，合成孕激素的异常激素和生物学活性通过改变受体表达，可能是影响乳腺细胞生长的一个重要因素。
