title: Different effects of corticotropin-releasing factor and urocortin 2 on apoptosis of prostate cancer cells in vitro.
abstract: Urocortin (Ucn), a corticotropin-releasing factor (CRF)-related neuropeptide binding both CRF type 1 receptor (CRFR1) and CRFR2, has recently been found in prostate cancer. However, no report has yet been known to elucidate the roles of Ucn in prostate cancer via the two receptors. In this study, the expression of both CRFR1 and CRFR2 in the mouse prostate cancer cell line RM-1 were detected and cellular apoptosis was monitored in the presence of CRF or Ucn2, the CRFR1- and CRFR2-selective agonist respectively. CRF promoted apoptosis while Ucn2 exerted the opposite effect. CRF reduced Bcl-2 expression, induced Bax expression, and hyperpolarized the mitochondrial membrane potential to activate caspase-9. On the contrary, Ucn2 increased Bcl-2 expression and decreased Bax expression, in which phosphorylation of Akt and cyclic AMP response element-binding (CREB) was involved. Pretreatment with phosphatidylinositide 3-kinase/Akt inhibitor (LY-294002) prior to Ucn2 led to downregulation of CREB phosphorylation and hence reduced Bcl-2 expression. These effects of CRF and Ucn2 were abolished by antalarmin (Anta) and antisauvagine-30, the CRFR1- and CRFR2-selective antagonist respectively. In LNCaP cell line, similar effects on cell apoptosis by CRF and Ucn2 were observed. In summary, our results demonstrated CRFR1 and CRFR2 expression in prostate cancer and indicated the opposite apoptotic roles of the two different CRFRs. These data may contribute to uncovering the pathophysiological function of endogenous Ucn in prostate tumorigenesis and progression.
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Lai
authors.initials: L
authors.lastname: Jin
authors.forename: Qichun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Juejin
authors.initials: J
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: Rongjian
authors.initials: R
authors.lastname: Zhang
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xu
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D054832:Urocortins / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002867:Chromones; D017362:Cyclic AMP Response Element-Binding Protein; D009025:Morpholines; D019253:Proto-Oncogene Proteins c-bcl-2; D054832:Urocortins; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003346:Corticotropin-Releasing Hormone; D051057:Proto-Oncogene Proteins c-akt