Imai A, Ohno T, Iida K, Fuseya T, Furui T, Tamaya T
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Cancer. 1994 Nov 1;74(9):2555-61. doi: 10.1002/1097-0142(19941101)74:9<2555::aid-cncr2820740925>3.0.co;2-x.
Gonadotropin-releasing hormone (Gn-RH) analogs have been used in the therapy of the endocrine-dependent cancers. The authors attempted to determine the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological cancers.
Experiments were performed on gynecologic tumors that had been surgically removed and their cloned cell lines. Gn-RHR was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic acid was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RHR sequence.
High affinity binding sites with nanomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6) and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-derived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumors.
We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies.
促性腺激素释放激素(Gn-RH)类似物已用于内分泌依赖性癌症的治疗。作者试图确定Gn-RH受体(Gn-RHR)在妇科癌症中的存在频率。
对手术切除的妇科肿瘤及其克隆细胞系进行实验。通过[3H]Gn-RH与质膜制剂的结合来表征Gn-RHR。使用根据已发表的人Gn-RHR序列合成的寡核苷酸引物,通过逆转录-聚合酶链反应测定Gn-RHR信使核糖核酸。
在来自子宫内膜(6/6)和子宫内膜癌(16/17)、子宫肌层(6/6)和子宫肌瘤(4/5)、上皮癌(21/23)以及卵巢间质瘤(3/3)的大部分标本(超过90%)中检测到具有纳摩尔范围Kd的高亲和力结合位点和Gn-RHR mRNA。宫颈癌或卵巢生殖细胞源性肿瘤中没有大量的Gn-RHR。克隆细胞系的结果与其各自的母肿瘤相同。
我们在源自子宫内膜和卵巢的多种癌症和组织中检测到Gn-RHR,但在子宫颈或生殖细胞源性肿瘤中未检测到。Gn-RH受体的表达增加了Gn-RH可能在这些癌症的生长中发挥直接调节作用的可能性,并为在这些恶性肿瘤中使用Gn-RH类似物的治疗方法提供了一个可能的攻击点。