Premium
Androgen‐independent growth is induced by neuropeptides in human prostate cancer cell lines
Author(s) -
Jongsma Johan,
Oomen Monique H.A.,
Noordzij Marinus A.,
Romijn Johannes C.,
van der Kwast Theodorus H.,
Schröder Fritz H.,
van Steenbrugge Gert J.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(20000101)42:1<34::aid-pros5>3.0.co;2-2
Subject(s) - lncap , endocrinology , medicine , androgen , biology , vasoactive intestinal peptide , androgen receptor , cell growth , gastrin releasing peptide , leydig cell , neuropeptide , prostate , prostate cancer , receptor , hormone , bombesin , cancer , luteinizing hormone , biochemistry
BACKGROUND Androgen‐independent growth leads to progressive prostate cancer after androgen‐ablation therapy. This may be caused by altered specificity of the androgen receptor (AR), by ligand‐independent stimulation of the AR, or by paracrine growth modulation by neuropeptides secreted by neuroendocrine (NE) cells. METHODS We established and characterized the androgen‐independent FGC‐DCC from the androgen‐dependent LNCaP fast growing colony (FGC) cell line. The androgen‐independent DU‐145, FGC‐DCC, and PC‐3, and the androgen‐dependent LNCaP and PC‐346C cell lines were used to study growth modulation of gastrin‐releasing peptide (GRP), calcitonin (CT), serotonin (5‐HT), and vasoactive intestinal peptide (VIP) by 3 H‐thymidine incorporation. Specificity of the growth‐modulating effects was tested with the anti‐GRP monoclonal antibody 2A11 and induction of cAMP by neuropeptides. RESULTS Androgen‐independent growth stimulation by neuropeptides was shown in DU‐145 and PC‐346C. 2A11 inhibited GRP‐induced 3 H‐thymidine incorporation in DU‐145 and PC‐346C and inhibited proliferation of the FGC‐DCC and PC‐3 cell lines. With some exceptions, cAMP induction paralleled growth stimulation. Dideoxyadenosine (DDA) inhibited the GRP‐induced growth effect in DU‐145 and PC‐346C, whereas oxadiazoloquinoxaline‐1‐one (ODQ) had no effect on 3 H‐thymidine incorporation. None of the neuropeptides stimulated growth of LNCaP, FGC‐DCC, or PC‐3. CONCLUSIONS GRP‐induced growth of DU‐145 and PC‐346C was specific and cAMP‐mediated. Androgen‐independent growth of FGC‐DCC cells was mainly due to an induction of Bcl‐2 expression and possibly through the activation of an autocrine and NE‐like pathway, as has been shown also for the PC‐3 cell line. Growth induction of non‐NE cells by neuropeptides could be a possible role for NE cells in clinical prostate cancer. Prostate 42:34–44, 2000. © 2000 Wiley‐Liss, Inc.