Adrenomedullin inhibits prostate cancer cell proliferation through a cAMP-independent autocrine mechanism

Biochemical and Biophysical Research Communications
Ibane AbasoloA Calvo

Abstract

Adrenomedullin (AM) is a multifunctional peptide expressed in the normal and malignant prostate, and in prostate cancer cells. To elucidate the potential role of AM in prostate cancer, we have transfected the human AM gene into PC-3, DU 145, and LNCaP prostate cancer cells. Northern blot, Western blot, and radioimmunoassay techniques confirmed an increase in the synthesis and secretion of the 6kDa mature peptide, in the AM-transfected clones. Proliferation and cell cycle assays demonstrated that AM overexpression inhibited cell proliferation in PC-3 and LNCaP cells through a G0/G1 cell cycle arrest, but not in DU 145 cells. In vivo growth assays also confirmed that, at least in PC-3, AM produced a very significant reduction of tumor volume. In addition, the three cell lines expressed the CL/RCP/RAMP-2 receptor complex by RT-PCR, which suggests that AM peptide acts through an autocrine loop in prostate cancer cells. Although cAMP elevation is the most common pathway involved in AM signalling, stimulation of PC-3, DU 145, and LNCaP with synthetic AM did not increase intracellular cAMP. However, short-term stimulation of PC-3 cells with synthetic AM increased ERK1/2 activation. On the contrary, long-term stimulation, or AM overexp...Continue Reading

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Citations

Dec 6, 2014·Journal of Translational Medicine·Ignacio M LarráyozAlfredo Martínez
Mar 20, 2016·Biochimica Et Biophysica Acta·Valerie Sloane JonesRuo-Pan Huang
Nov 22, 2005·Regulatory Peptides·Ibane AbasoloAlfonso Calvo
Mar 22, 2006·Expert Opinion on Therapeutic Targets·Mario A GarcíaAlfredo Martínez
Feb 10, 2007·International Journal of Cancer. Journal International Du Cancer·Shereen KelegJörg Kleeff
Dec 3, 2014·Breast Cancer Research : BCR·Valerie A SiclariJohn M Chirgwin
Sep 17, 2005·Cancer Research·Srinivasulu ChigurupatiGirish Shah

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