Parathyroid hormone-related protein is not an autocrine growth factor for normal prostatic epithelial cells

Peehl, Donna M.; Edgar, Michelle G.; Cramer, Scott D.; Deftos, Leonard J.

doi:10.1002/(sici)1097-0045(19970401)31:1<47::aid-pros8>3.0.co;2-f

Cited by 16 publications

(1 citation statement)

References 30 publications

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“…Neuropeptides are growth factors either eutopically or ectopically produced by these NE cells. Serotonin (5-HT) [7][8][9], bombesin or gastrin-releasing peptide (GRP) [10][11][12][13][14][15], vasoactive intestinal peptide (VIP) [16,17], calcitonin (CT) [18][19][20][21], parathyroid hormone-related protein (PTHRP) [22][23][24][25], and somatostatin (SMS) [26] are all examples of growthmodulating neuropeptides in neoplasias of the lung, intestine, pancreas, prostate, and other epithelia [27,28]. Most of the known neuropeptides act via cAMP induction through stimulation of adenyl cyclase [29][30][31] and Ca 2+ mobilization [32][33][34][35], or via cGMP-coupled receptor proteins [36].…”

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confidence: 99%

Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines

et al. 2000

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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 3H‐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 3H‐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 3H‐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.

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