The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary.
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.
Kakar
S S
SS
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294.
Grizzle
W E
WE
Neill
J D
JD
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000737:chemistry*; D010902:Pituitary Gland / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D011966:Receptors, LHRH / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D011966:Receptors, LHRH; D012194:RNA-Directed DNA Polymerase