Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line
Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line
复制标题
雌激素受体拮抗剂对催乳素瘤MMQ细胞生物学行为及生长因子表达的影响
DOI：
10.1007/s11060-010-0326-2
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Zhang, Yazhuo
中科院分区：
文献类型：
--
作者：
Lv, Hongtao;Li, Chuzhong;Zhang, Yazhuo
雌激素与垂体泌乳素瘤之间的关系已被充分证实。雌激素的生物学效应主要由雌激素受体α (ER α)介导。多项证据表明垂体瘤转化基因（PTTG）、碱性成纤维细胞生长因子（bFGF）、转化生长因子β 1 （TGF β 1）、转化生长因子β 3 （TGF β 3）、转化生长因子β受体II型（TGF β RII）等生长因子在雌激素诱导的催乳素瘤发病过程中发挥重要作用，但ER α与这些生长因子之间的关系尚不清楚。本研究旨在探讨在缺乏雌激素的情况下，ER α在MMQ细胞增殖、泌乳素（PRL）分泌及上述生长因子表达中的功能作用，并探讨使用雌激素受体拮抗剂治疗催乳素瘤的可行性。Fulvestrant是一种“纯”抗雌激素，没有任何雌激素样活性，用于阻断MMQ细胞系中ER α的表达。采用CellTiter 96（A (R)）水溶液细胞增殖法（MTS）和酶联免疫吸附法（ELISA）检测MMQ细胞的增殖和PRL分泌。实时聚合酶链反应（real-time polymerase chain reaction， PCR）和Western blot检测ER α、PTTG、bFGF、TGF β 1、TGF β 3、TGF β RII水平。在没有雌激素的情况下，Fulvestrant显著抑制细胞增殖（高达60.80%）和PRL分泌（高达77.95%），并改变TGF β 3和TGF β RII的表达。综上所述，ER α在垂体泌乳素瘤的增殖和PRL分泌中起着重要的功能作用，即使在无雌激素的情况下也能改变某些生长因子的表达。Fulvestrant可能是治疗这类肿瘤的有效疗法。
The relationship between estrogen and pituitary prolactinoma is well documented. The biological effects of estrogen are mainly mediated by estrogen receptor alpha (ER alpha). Several lines of evidence demonstrate that growth factors such as pituitary tumor transforming gene (PTTG), basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1), transforming growth factor beta 3 (TGF beta 3), and transforming growth factor beta receptor type II (TGF beta RII) play an important role in prolactinoma pathogenesis induced by estrogen, but the relationship between ER alpha and such growth factors is still unclear. The aims of this study are to investigate the functional role of ER alpha in proliferation, prolactin (PRL) secretion, and expression of the above-mentioned growth factors in MMQ cells in the absence of estrogen and to discuss the feasibility of using an estrogen receptor antagonist to treat prolactinoma. Fulvestrant, a "pure" antiestrogen without any estrogen-like activity, was used to block expression of ER alpha in the MMQ cell line. Proliferation and PRL secretion of MMQ cells were measured using CellTiter 96(A (R)) AQueous One Solution Cell Proliferation Assay (MTS) and the enzyme-linked immunosorbent assay (ELISA) method. Levels of ER alpha, PTTG, bFGF, TGF beta 1, TGF beta 3, and TGF beta RII were analyzed by real-time polymerase chain reaction (PCR) and Western blot. Fulvestrant significantly inhibited cell proliferation (up to 60.80%) and PRL secretion (up to 77.95%), and changed expression of TGF beta 3 and TGF beta RII in the absence of estrogen. In conclusion, ER alpha plays an important functional role in proliferation and PRL secretion of pituitary prolactinomas and also can change expression of some growth factors even under the condition of no estrogen. Fulvestrant could potentially be an effective therapy for treating such tumors.