title: Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors.
abstract: The molecular mechanisms involved in differentiation of prostate cancer cells to a neuroendocrine (NE) cell phenotype are not well understood. Here we used the androgen-dependent human prostate cancer cell line LNCaP to perform a systematic and broad analysis of the expression, pharmacology, and functionality of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptors. Reverse transcription polymerase chain reaction experiments, together with pharmacological approaches with a set of specific agonists and antagonists, demonstrated the presence of the three VIP/PACAP receptor subtypes (PAC1, VPAC1, and VPAC2 with a major role for VPAC1, acting through adenylate cyclase (AC) stimulation. An essentially similar pattern was observed by NE differentiated cells (4 days after serum deprivation) in spite of the important morphological changes observed. However, the expression of the prostate-specific antigen (PSA) decreased in NE cells (and increased again by dihydrotestosterone, DHT, treatment). The present demonstration of the induction of NE transdifferentiation in LNCaP cells by increasing concentrations of VIP adds value to previous observations on the role of cAMP in this process, an interesting topic in the comprehension of the molecular changes that are involved in the progression of prostate cancer to androgen independence.
authors.affiliation: Department of Biochemistry and Molecular Biology, Universidad de Alcalá, 28871, Alcalá de Henares, Spain.
authors.forename: M G
authors.initials: MG
authors.lastname: Juarranz
authors.forename: O
authors.initials: O
authors.lastname: Bolaños
authors.forename: I
authors.initials: I
authors.lastname: Gutiérrez-Cañas
authors.forename: E A
authors.initials: EA
authors.lastname: Lerner
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
authors.forename: M J
authors.initials: MJ
authors.lastname: Carmena
authors.forename: J C
authors.initials: JC
authors.lastname: Prieto
authors.forename: N
authors.initials: N
authors.lastname: Rodríguez-Henche
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D001667:Binding, Competitive; D002454:Cell Differentiation; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: C495401:ADCYAP1 protein, human; C495503:ADCYAP1R1 protein, human; D016895:Culture Media, Serum-Free; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012334:RNA, Neoplasm; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495506:VIPR1 protein, human; C495509:VIPR2 protein, human; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases