Journal
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
Volume 27, Issue 1, Pages 27-45Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10799890601087487
Keywords
prostate cancer; adrenergic receptor; intracellular localization; DU145; PC3; TRAMP
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The function and distribution of alpha(1)-adrenergic receptor (AR) subtypes in prostate cancer cells is well characterized. Previous studies have used RNA localization or low-avidity antibodies in tissue or cell lines to determine the alpha(1)-AR subtype and suggested that the alpha(1A)-AR is dominant. Two androgen-insensitive, human metastatic cancer cell lines DU145 and PC3 were used as well as the mouse TRAMP C1-C3 primary and clonal cell lines. The density of alpha(1)-ARs was determined by saturation binding and the distribution of the different alpha(1)-AR subtypes was examined by competition-binding experiments. In contrast to previous studies, the major alpha(1)-AR subtype in DU145, PC3 and all of the TRAMP cell lines is the alpha(1B)-AR. DU145 cells contained 100% of the alpha(1B)-AR subtype, whereas PC3 cells were composed of 21% alpha(1A)-AR and 79% alpha(1B)-AR. TRAMP cell lines contained between 66% and 79% of the alpha(1B)-AR with minor fractions of the other two subtypes. Faster doubling time in the TRAMP cell lines correlated with decreasing alpha(1B)-AR and increasing alpha(1A)- and alpha(1D)-AR densities. Transfection with EGFP-tagged alpha(1B)-ARs revealed that localization was mainly intracellular, but the majority of the receptors translocated to the cell surface after extended preincubation (18 hr) with either agonist or antagonist. Localization was confirmed by ligand-binding studies and inositol phosphate assays where prolonged preincubation with either agonist and/or antagonist increased the density and function of alpha(1)-ARs, suggesting that the native receptors were mostly intracellular and nonfunctional. Our studies indicate that alpha(1B)-ARs are the major alpha(1)-AR subtype expressed in DU145, PC3, and all TRAMP cell lines, but most of the receptor is localized in intracellular compartments in a nonfunctional state, which can be rescued upon prolonged incubation with any ligand.
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