THE NUCLEOTIDE-SEQUENCES OF HUMAN GNRH RECEPTORS IN BREAST AND OVARIAN-TUMORS ARE IDENTICAL WITH THAT FOUND IN PITUITARY

THE NUCLEOTIDE-SEQUENCES OF HUMAN GNRH RECEPTORS IN BREAST AND OVARIAN-TUMORS ARE IDENTICAL WITH THAT FOUND IN PITUITARY
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DOI:
10.1016/0303-7207(94)90196-1
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发表时间:
1994-12-01
影响因子:
4.1
通讯作者:
NEILL, JD
NEILL, JD
中科院分区:
医学2区
文献类型:
--
作者:
KAKAR, SS;GRIZZLE, WE;NEILL, JD

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GnRH激动剂和拮抗剂对体外培养的荷尔蒙相关肿瘤细胞的生长抑制作用表明,GnRH激动剂和拮抗剂对肿瘤细胞的生长和增殖有直接影响,这种作用可能是通过肿瘤细胞中的GnRH受体实现的。然而,这些肿瘤中存在的GnRH受体的性质存在争议,为了确定这些肿瘤中GnRH受体的分子特征,我们使用逆转录/聚合酶链式反应(RT/PCR)技术克隆了这些受体。从人垂体促性腺激素释放激素受体(GnRH)基因序列中筛选出引物,扩增出其开放阅读框及其部分5‘和3’非翻译序列。来自乳腺肿瘤细胞系(MCF-7)和卵巢肿瘤的GnRH受体cDNAs的核苷酸序列与人垂体GnRH受体的核苷酸序列一致,后者以高亲和力结合GnRH。GnRH受体在人的垂体、乳腺、乳腺肿瘤、卵巢、卵巢肿瘤、前列腺癌、前列腺癌以及乳腺肿瘤细胞系(MCF-7和MDA-MB 468)和前列腺肿瘤细胞系(PC-3和LNCaP)中均有表达。这些发现表明,代表GnRH受体(与GnRH高亲和力结合)的垂体形式的mRNA也在某些正常组织和激素相关的人类肿瘤及其衍生的肿瘤细胞系中表达。
Inhibition of the growth of hormone related human tumor cells in vitro by GnRH agonists and antagonists suggests a direct effect on cell growth and proliferation, and this effect may be achieved through its receptors present in tumor cells. However, the nature of the GnRH receptors present in these tumors is controversial, To determine the molecular characteristics of GnRH receptors in such tumors, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique to clone these receptors. Primers were selected from the human pituitary GnRH receptor cDNA sequence to amplify the open reading frame and parts of its 5' and 3'-untranslated sequences. Nucleotide sequencing of the GnRH receptor cDNAs from a breast tumor cell line (MCF-7) and from an ovarian tumor showed identity with that of the human pituitary GnRH receptor which binds GnRH with high affinity. GnRH receptor mRNA was found to be expressed in human pituitary, breast, breast tumor, ovary, ovarian tumor, prostate, prostate tumor and in breast tumor cell lines (MCF-7 and MDA-MB 468) and prostate tumor' cell lines (PC-3 and LNCaP). These findings demonstrate that a mRNA representing the pituitary form of the GnRH receptor (which shows high affinity binding with GnRH) is also expressed in certain normal tissues and in hormone related human tumors and tumor cell lines derived from them.