Kakar S S, Grizzle W E, Neill J D
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294.
Mol Cell Endocrinol. 1994 Dec;106(1-2):145-9. doi: 10.1016/0303-7207(94)90196-1.
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.
促性腺激素释放激素(GnRH)激动剂和拮抗剂在体外对激素相关的人类肿瘤细胞生长具有抑制作用,这表明其对细胞生长和增殖有直接影响,且这种作用可能是通过肿瘤细胞中存在的受体实现的。然而,这些肿瘤中存在的GnRH受体的性质存在争议。为了确定此类肿瘤中GnRH受体的分子特征,我们使用逆转录酶/聚合酶链反应(RT/PCR)技术来克隆这些受体。从人垂体GnRH受体cDNA序列中选择引物,以扩增开放阅读框及其5'和3'非翻译序列的部分。来自乳腺癌细胞系(MCF-7)和卵巢肿瘤的GnRH受体cDNA的核苷酸测序显示,其与高亲和力结合GnRH的人垂体GnRH受体相同。发现GnRH受体mRNA在人垂体、乳腺、乳腺肿瘤、卵巢、卵巢肿瘤、前列腺、前列腺肿瘤以及乳腺癌细胞系(MCF-7和MDA-MB 468)和前列腺肿瘤细胞系(PC-3和LNCaP)中表达。这些发现表明,代表垂体形式的GnRH受体(与GnRH具有高亲和力结合)的mRNA也在某些正常组织以及激素相关的人类肿瘤和源自它们的肿瘤细胞系中表达。