The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues.
Various attempts to detect human pituitary growth hormone-releasing hormone receptor (pGHRH-R) in neoplastic extrapituitary tissues have thus far failed. Recently, four splice variants (SVs) of GHRH-R have been described, of which SV1 has the highest structural homology to pGHRH-R and likely plays a role in tumor growth. The aim of this study was to reinvestigate whether human tumors and normal human extrapituitary tissues express the pGHRH-R and to corroborate our previous findings on its SVs. Thus, we developed a real-time PCR method for the detection of the mRNA for the pGHRH-R, its SVs, and the GHRH peptide. Using real-time PCR, Western blotting, and radioligand-binding assays, we detected the mRNA for pGHRH-R and pGHRH-R protein in various human cancer cell lines grown in nude mice and in surgical specimens of human lung cancers. The expression of mRNA for SVs of pGHRH-R and GHRH was likewise found in xenografts of human non-Hodgkin's lymphomas, pancreatic cancer, glioblastoma, small-cell lung carcinomas, and in human nonmalignant prostate, liver, lung, kidney, and pituitary. Western blots showed that these normal and malignant human tissues contain SV1 protein and immunoreactive GHRH. Our results demonstrate that some normal human tissues and tumors express mRNA and protein for the pGHRH-R and its splice variants. These findings confirm and extend the concept that GHRH and its receptors play an important role in the pathophysiology of human cancers.
Havt
Alexandre
A
Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112-1262, USA.
Schally
Andrew V
AV
Halmos
Gabor
G
Varga
Jozsef L
JL
Toller
Gabor L
GL
Horvath
Judit E
JE
Szepeshazi
Karoly
K
Köster
Frank
F
Kovitz
Kevin
K
Groot
Kate
K
Zarandi
Marta
M
Kanashiro
Celia A
CA
D017398:Alternative Splicing / Q000235:genetics*; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D011869:Radioligand Assay; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor