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In Vitro Expression of Endothelin-1 (ET-1) and the ET_A and ET_B ET Receptors by the Prostatic Epithelium and Stroma¹

University Department of Surgery (E.S.G., F.K.H.)/Medicine (B.C.W.), University of Edinburgh, Western General Hospital, Edinburgh, Scotland EH4 2XU; and Rhône-Poulenc Rorer Limited (T.B., A.R.), Dagenham Research Centre, Dagenham, Essex, United Kingdom RM10 7XS

Address all correspondence and requests for reprints to: Dr. E. S. Grant, University Department of Surgery, Western General Hospital, Crewe Road South, Edinburgh, United Kingdom EH4 2XU.

RT-PCR analysis of total RNA prepared from the prostate cancer cell lines DU145 and PC3 and from primary epithelial cells indicated the presence of endothelin-1 (ET-1) messenger RNA (mRNA). Neither the LNCaP cell line nor primary prostatic stromal cells possess ET-1 mRNA transcripts. Seventy-two-hour-conditioned media derived from DU145, PC3, and primary epithelia contain immunoreactive ET concentrations equivalent to 0.814 ± 0.048, 0.330 ± 0.050, and 0.856 ± 0.055 fmol/mL/10⁶ cells after 72 h, respectively. Basal immunoreactive ET secretion was exhibited by LNCaP (0.029 ± 0.009 fmol/mL/10⁶ cells after 72 h) and stromal cells (0.067 ± 0.007 fmol/mL/10⁶ cells after 72 h). Examination of ET_A and ET_B gene expression by RT-PCR demonstrates that ET receptor mRNA is almost completely undetectable in the prostate cancer cell lines. Both ET_A and ET_B mRNAs are detectable in primary cultures of prostatic epithelia and stroma. Competitive binding studies demonstrate a single class of binding site in both primary benign epithelia (dissociation constant = 1.85 x 10^-10 mol/L; maximal binding capacity = 2.7 x 10⁴ binding sites/cell), and stroma (dissociation constant = 1.93 x 10^-10 mol/L; maximal binding capacity = 3.7 x 10⁵ binding sites/cell). Use of selective ET receptor antagonists confirmed that the predominant stromal receptor subtype expressed in vitro is ET_B. This receptor seems not to be coupled to mitogenic pathways because no growth response to exogenous ET-1 or cooperation between ET-1 and bFGF could be observed. Similarly, no effect of ET-1 or the ET-converting enzyme inhibitor, phosphoramidon, on benign epithelial cells could be observed over a 4-day period.

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