Kakar S S
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294-0005, USA.
Cancer Res. 1998 Oct 15;58(20):4558-60.
The mechanism by which gonadotropin-releasing hormone (GnRH) agonists and antagonists inhibit tumor cell growth and proliferation is controversial. Direct mediation of the antitumor effects through the high-affinity GnRH receptors has been questioned because of the low level of expression of receptors on the tumor cells. We have developed a human kidney embryonic cell line (EcRG293) that expresses high-affinity GnRH receptor under the control of an inducible promoter activated by muristerone A. Treatment of this cell line with either GnRH agonist (D-Lys6)GnRH or GnRH antagonist (Antide) resulted in a significant, time-dependent decrease in cell proliferation in muristerone A-induced cells but not in the uninduced cells, which do not express the GnRH receptor. These data suggest strongly that the antitumor effect of GnRH agonists and antagonist is specific, direct, and mediated through high-affinity GnRH receptors present on the cell membranes of tumor cells.
促性腺激素释放激素（GnRH）激动剂和拮抗剂抑制肿瘤细胞生长和增殖的机制存在争议。由于肿瘤细胞上受体表达水平较低，通过高亲和力GnRH受体直接介导抗肿瘤作用受到质疑。我们构建了一种人肾胚胎细胞系（EcRG293），该细胞系在由醋酸孕诺酮激活的诱导型启动子控制下表达高亲和力GnRH受体。用GnRH激动剂（D-Lys6）GnRH或GnRH拮抗剂（Antide）处理该细胞系，在醋酸孕诺酮诱导的细胞中导致细胞增殖显著且呈时间依赖性下降，但在未诱导的、不表达GnRH受体的细胞中则无此现象。这些数据有力地表明，GnRH激动剂和拮抗剂的抗肿瘤作用是特异性的、直接的，并且是通过肿瘤细胞膜上存在的高亲和力GnRH受体介导的。
