PGRMC1 can trigger estrogen-dependent proliferation of breast cancer cells: estradiol vs. equilin vs. ethinylestradiol

Abstract

Objective: Previous studies have shown that progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer tissue can predict a worse prognosis for breast cancer patients. Moreover, we demonstrated that PGRMC1 can increase the proliferation of progestogens. However, the role of PGRMC1 in terms of estrogen-induced proliferation and comparing different estrogens is still unclear.

Methods: Non-transfected and PGRMC1-transfected T-47D cells were stimulated with estradiol (E2), with equilin (EQ), or with ethinylestradiol (EE) at 1, 10, and 100 nmol/l. Increase of proliferation was compared with a control (without estrogens) and with the estrogen-induced stimulation in empty vector cells vs. PGRMC1-transfected cells.

Results: The empty vector cells showed significant proliferation (12–15%) with all three estrogens only at the highest concentration, with no relevant differences between the estrogens. PGRMC1-transfected cells showed about three-fold higher proliferation (29–66%), whereby E2 elicited the strongest and EE the lowest proliferating effects, significantly lower compared to E2 and also compared to EQ. No significant differences were seen between E2 and EQ.

Conclusions: PGRMC1 increases strongly the estrogen-dependent breast cell proliferation. The proliferating effects of EE may be lower compared to E2 and EQ. This could have importance in comparing hormone therapy and contraception. Thus, PGRMC1 not only could predict the risk using progestogens but also of different estrogens.

Chinese abstract

目的：先前的研究已表明, 乳腺癌组织中表达的孕激素受体膜组分1（PGRMC1）可预测乳腺癌患者预后较差。此外, 我们还证明了PGRMC1可以促进孕激素的增殖。然而, PGRMC1在雌激素诱导增殖和比较不同雌激素的增殖作用方面尚不清楚。

方法：分别用雌二醇（E2）、马烯雌酮（EQ）或炔雌醇（EE）分别于1、10、100nmol/l水平刺激转染PGRMC1和未转染的T-47D细胞。与对照组（不含雌激素）和空白载体细胞与转染PGRMC1的细胞相比, 雌激素诱导的细胞增殖增加。转染PGRMC1的细胞与空载体细胞在雌激素诱导刺激下与对照组（无雌激素）相比, 乳腺癌细胞增殖增加。

结果：三种雌激素均以最高浓度刺激时, 空载体细胞增殖明显（12-15%）, 且各雌激素处理组差异无统计学意义。转染PGRMC1的细胞增殖能力约为正常细胞的3倍（29-66%）, 其中E2诱导的增殖能力最强, EE诱导的增殖能力最低, 明显低于E2, 也低于EQ。而E2与EQ之间无明显统计学差异。

结论：PGRMC1能明显促进雌激素依赖性乳腺癌细胞增殖。EE的促增殖效应可低于E2和EQ, 这对激素治疗和避孕方面有重要意义。因此, PGRMC1不仅可以预测使用孕激素的风险, 还可以预测不同雌激素的风险。

Keywords:

• Breast cancer
• cell proliferation
• equilin
• estradiol
• ethinylestradiol
• progesterone receptor membrane component 1

Potential conflict of interest

The authors have declared no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81671411]; Beijing Natural Science Foundation [grant number 7162062]; Beijing Municipal Administration of Hospitals’ Ascent Plan [Code: DFL20181401]; Beijing Nova Program Interdisciplinary Cooperation Projects [grant number Z161100004916045]; Beijing Municipality Health Technology Highlevel Talent [grant number 2014-2-016].