title: Differential effects of exogenous and autocrine growth hormone on LNCaP prostate cancer cell proliferation and survival.
abstract: The prostate gland is regulated by multiple hormones and growth factors that may also affect prostate tumorigenesis. Growth hormone (GH) contributes to prostate development and function, but the direct effects of GH on prostate cancer cells are not well understood. The expression of endogenous GH in prostate cancer cell lines has also been observed, suggesting the potential for an effect of autocrine GH. In the present study, we measure the levels of GH and GH receptor (GHR) mRNA in multiple prostate cancer and normal prostate-derived cell lines, and compare the effects of exogenous and autocrine GH on LNCaP prostate cancer cell proliferation and apoptosis, and the associated signal transduction pathways. We found that GHR and GH expression were higher in the prostate cancer cell lines, and that exogenous GH increased LNCaP cell proliferation, but had no effect on apoptosis. In contrast, autocrine GH overexpression reduced LNCaP cell proliferation and increased apoptosis. The distinct actions of exogenous and autocrine GH were accompanied by differences in the involvement of GHR-associated signal transduction pathways, and were paralleled by an alteration in the subcellular localization of GHR, in which autocrine GH appeared to sequester GHR in the Golgi and endoplasmic reticulum. This alteration of GHR trafficking may underlie a distinct mode of GH-mediated signaling associated with the effect of autocrine GH. These findings clarify the potential effects of GH on prostate cancer cell function, and indicate that the activity of autocrine GH may be distinct from that of endocrine GH in prostate cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA.
authors.forename: Alona O
authors.initials: AO
authors.lastname: Nakonechnaya
authors.forename: Holly S
authors.initials: HS
authors.lastname: Jefferson
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.forename: Brian M
authors.initials: BM
authors.lastname: Shewchuk
mesh_terms: D017209:Apoptosis; D019898:Autocrine Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019382:Human Growth Hormone / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D021381:Protein Transport; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone