University Women's Hospital, Tuebingen, Germany.
Menopause. 2011 Aug;18(8):845-50. doi: 10.1097/gme.0b013e31820e5ac5.
Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1.
MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M).
E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells.
Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.
乳腺癌风险仍然是激素治疗和口服避孕药的一个重要话题。越来越多的证据表明孕激素可能发挥关键作用。在乳腺癌中表达的孕激素受体膜成分 1（PGRMC1）可能在肿瘤发生中很重要，因此可能会增加乳腺癌的风险。本项目的目的是研究不同雌二醇（E2）浓度以及添加两种孕激素对过表达 PGRMC1 的 MCF-7 乳腺癌细胞的影响。
MCF-7 细胞用 PGRMC1 表达质粒（MCF-7/PGRMC1-3HA[WT-12]）稳定转染。为了测试 E2 和孕激素对细胞增殖的影响，用不同浓度的 E2（10 和 10 M）单独以及与孕酮和醋酸甲地孕酮（各 10 M）联合刺激 MCF-7 和 WT-12 细胞。
E2 对两种细胞系均表现出浓度依赖性的增殖作用，在 WT-12 细胞中更为明显（50%对 200%）。这种作用可以被 E2 拮抗剂氟维司群完全阻断。孕酮的添加对 E2 诱导的作用没有影响，而醋酸甲地孕酮在低 E2 浓度下增强了 E2 诱导的作用，在 WT-12 细胞中更为明显。在 MCF-7 细胞中，数值在 20%到 40%之间，在 WT-12 细胞中在 60%到 250%之间。
PGRMC1 的过表达使 MCF-7 乳腺癌细胞系对雌二醇的增殖反应变得敏感。孕激素对乳腺癌发生的影响可能取决于用于激素治疗或口服避孕药的特定孕激素。
