GONADOTROPIN-RELEASING-HORMONE (GNRH)-BINDING SITES IN HUMAN-BREAST CANCER CELL-LINES AND INHIBITORY EFFECTS OF GNRH ANTAGONISTS
GONADOTROPIN-RELEASING-HORMONE (GNRH)-BINDING SITES IN HUMAN-BREAST CANCER CELL-LINES AND INHIBITORY EFFECTS OF GNRH ANTAGONISTS
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DOI：
10.1210/jcem-64-3-425
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发表时间：
1987-03-01
影响因子：
5.8
通讯作者：
MILLAR, RP
中科院分区：
文献类型：
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作者：
EIDNE, KA;FLANAGAN, CA;MILLAR, RP
GnRH结合位点先前已在人乳腺肿瘤中描述，并且GnRH激动剂已显示出抑制MCF-7人乳腺癌细胞系的生长。我们研究了ZR-75-1、MDA-MB-231、Sk Br 3、MDA-MB-157和MCF-7人乳腺癌细胞系中GnRH结合位点的存在，以及GnRH类似物对[3 H]胸苷和14 C标记氨基酸掺入DNA和蛋白质的影响。特异性GnRH结合位点存在于所有五种人乳腺癌细胞系的膜制剂中。在三种细胞系中的研究表明低亲和力（Kd，1.6-3.0 × 10 - 6）。10-6 M）GnRH结合类似于人胎盘和黄体中报道的结合。相反，人垂体GnRH受体具有高亲和力（Kd，4.8 × 10 - 6）。10-9 M）。乳腺癌细胞GnRH结合位点也与垂体受体不同，因为它们无法区分GnRH和超活性类似物。[125 I] GnRH类似物与ZR-75-1乳腺癌细胞和垂体膜的结合受到各种阳离子的类似影响。GnRH拮抗剂迅速抑制[3 h]胸苷掺入DNA（3小时内），这种作用是可逆的。GnRH拮抗剂也抑制细胞生长，但仅在6天后。GnRH激动剂不改变胸苷掺入或生长。目前在乳腺癌细胞系中观察到的低亲和力GnRH结合位点和GnRH拮抗剂的抑制作用表明，GnRH样肽在乳腺细胞中可能具有自分泌调节作用。
GnRH-binding sites have previously been described in human breast tumors, and a GnRH agonist has been shown to inhibit growth of the MCF-7 human breast cancer cell line. We have investigated the presence of GnRH-binding sites in ZR-75-1, MDA-MB-231, Sk Br 3, MDA-MB-157, and MCF-7 human breast cancer cell lines and the effect of GnRH analogs on the incorporation of [3H]thymidine and 14C-labeled amino acids into DNA and protein. Specific GnRH-binding sites were present in membrane preparations of all five human breast carcinoma cell lines. Studies in three cell lines indicated low affinity (Kd, 1.6-3.0 .times. 10-6 M) GnRH binding similar to that reported in human placenta and corpus luteum. In contrast, human pituitary GnRH receptors were of high affinity (Kd, 4.8 .times. 10-9 M). Breast carcinoma cell GnRH-binding sites also differed from the pituitary receptor in their inability to discriminate between gnRH and superactive analogs. Binding of [125I] GnRH analog to ZR-75-1 breast cancer cells and pituitary membranes was affected similarly by various cations. GnRH antagonists rapidly inhibited [3h]thymidine incorporation into DNA (within 3 hr), and this effect was reversible. GnRH antagonists also inhibited cell growth, but only after 6 days. GnRH agonists did not alter either thymidine incorporation or growth. The present observations of low affinity GnRH-binding sites in breast cancer cell lines and inhibitory effects of GnRH antagonists point to the possibility of an autocrine regulatory role of GnRH-like peptides in mammary cells.