Research article summary (published 16 Jun 2009):

Regulation of growth hormone receptors in human prostate cancer cell lines.

Full Abstract

We previously demonstrated the gene expression of two growth hormone (GH) receptor (GHR) isoforms in prostate cancer (PCa) patient tissues and human PCa cell lines. In that initial study, we characterized LNCaP cell GH binding characteristics to GHR and its activation of relevant signal transduction pathways. We now show that GH binding to GHR and GHR mRNA expression in the cell lines studied are hormonally regulated. In the androgen-dependent LNCaP cells, the potent, specific and stable androgen analogue, mibolerone, caused a time- and biphasic dose-dependent, stimulation of (125)I-hGH specific binding to cells cultured in serum-free medium (SFM); however, when LNCaP cells were grown in chemically defined Gc full medium, long-term mibolerone-induced inhibition was observed. This effect of Gc on the androgen response was mimicked by the triiodothyronine (T(3)) contained in GC. In contrast, oestradiol (E(2)), cortisol, and insulin-like growth factor (IGF)-I and -II all caused stimulation of GH binding. Furthermore, we also observed homologous and heterologous, isoform- and cell-type-specific regulation of GHR mRNA expression in all three cell lines. In LNCaP cells, GH caused stimulation of both GHR mRNA and of its exon 9-truncated isoform, GHR(tr); however, mibolerone, E(2) and T(3) all stimulated GHR(tr) mRNA more potently than they did GHR. In androgen-independent PC3 cells, GH stimulated GHR(tr) expression, but almost not GHR, while in contrast, in androgen-independent DU145 cells, GH caused a clear reduction in GHR and less so in GHR(tr). The differential regulation of GHR isoform gene expression in human PCa cell lines and of GHR functional capacity (GH binding), by hormones and growth factors relevant to disease progression, suggests that GHR may prove to be an additional therapeutic target to slow down/prevent progression of human prostate cancer.

Author information

Author/s: Bidosee, Maslama (M); Karry, Rachel (R); Weiss-Messer, Esther (E); Barkey, Ronnie J (RJ);

Affiliation: Department of Molecular Pharmacology, The Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol), published in Ireland. (Language: eng)

Reference: 2009-Oct; vol 309 (issue 1-2) : pp 82-92

Dates: Created 2009/08/03; Completed 2009/10/26;

PMID: 19540305, status: MEDLINE (last retrieval date: 10/26/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Androgen Antagonists - pharmacology Androgens - pharmacology Cell Line, Tumor Culture Media Culture Media, Serum-Free Estradiol - pharmacology Gene Expression Regulation, Neoplastic - drug effects Human Growth Hormone - metabolism Humans Hydrocortisone - pharmacology Insulin-Like Growth Factor I - pharmacology

Insulin-Like Growth Factor I - pharmacology Insulin-Like Growth Factor II - pharmacology Iodine Radioisotopes Male Mutant Proteins - metabolism Nandrolone - analogs & derivatives; pharmacology Prostatic Neoplasms - genetics; metabolism Protein Isoforms - genetics; metabolism RNA, Messenger - genetics; metabolism Receptors, Somatotropin - genetics; metabolism Triiodothyronine - pharmacology

Associated Chemicals: Androgen Antagonists (0) ; Androgens (0) ; Culture Media (0) ; Culture Media, Serum-Free (0) ; Iodine Radioisotopes (0) ; Mutant Proteins (0) ; Protein Isoforms (0) ; RNA, Messenger (0) ; Receptors, Somatotropin (0) ; Human Growth Hormone (12629-01-5) ; mibolerone (3704-09-4) ; Nandrolone (434-22-0) ; Hydrocortisone (50-23-7) ; Estradiol (50-28-2) ; Insulin-Like Growth Factor I (67763-96-6) ; Insulin-Like Growth Factor II (67763-97-7) ; Triiodothyronine (6893-02-3)

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