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Comparative Study
. 2005 Nov 29;102(48):17424-9.
doi: 10.1073/pnas.0506844102. Epub 2005 Nov 18.

The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues

Alexandre Havt  1 , Andrew V Schally, Gabor Halmos, Jozsef L Varga, Gabor L Toller, Judit E Horvath, Karoly Szepeshazi, Frank Köster, Kevin Kovitz, Kate Groot, Marta Zarandi, Celia A Kanashiro
Affiliations
Comparative Study

The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues

Alexandre Havt et al. Proc Natl Acad Sci U S A. .

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
Western blot analysis of SV1 (A), pGHRH-R (B), and GHRH (C), with β-actin as control in two samples each of xenografted tumor tissues of human non-Hodgkin's lymphomas (HT and RL), pancreatic cancer (MiaPaCa-2), glioblastoma (DBTRG-05), and small cell lung cancers (H82 and H345) and in three human NSCLC specimens (H1, H2, and H4) and normal human samples of prostate, kidney, lung, liver, and pituitary. All immunoreactive signals were detected with the purified antisera for SV1-SV2-SV4 (A), pGHRH-R (B), and a commercial antiserum for GHRH (C). The molecular masses are shown.
Fig. 2.
Fig. 2.
Western blot analysis of SV1-SV2-SV4 (A and B) and pGHRH-R (C and D) in samples of normal human prostate (P), kidney (K), lung (L), liver (Li), and pituitary (Pi) tissue. (A and C) Blots incubated with the purified antisera for SV1-SV2-SV4 (A) and pGHRH-R (C). (B and D) Blots with the antisera that were depleted by incubation with specific blocking peptides.
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References

    1. Schally, A. V. (2003) in Peptides and Nonpeptides of Neuroendocrine and Oncological Relevance, ed. Muller, E. E. (Springer, Milan), pp. 83-98.
    1. Schally, A. V. & Varga, J. L. (1999) Trends Endocrinol. Metab. 10, 383-391. - PubMed
    1. Schally, A. V., Comaru-Schally, A. M., Nagy, A., Kovacs, M., Szepeshazi, K., Plonowski, A., Varga, J. L. & Halmos, G. (2001) Front. Neuroendocrinol. 22, 248-291. - PubMed
    1. Szepeshazi, K., Schally, A. V., Groot, K., Armatis, P., Hebert, F. & Halmos, G. (2000) Eur. J. Cancer 36, 128-136. - PubMed
    1. Csernus, V. J., Schally, A.V., Kiaris, H. & Armatis, P. (1999) Proc. Natl. Acad. Sci. USA 96, 3098-3103. - PMC - PubMed

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