In low invasive LNCaP cells, 50 μmol/L ISO or 100 nmol/L thyroxine (T4) induced the acquisition of NE-like morphology (phase-contrast microscopy), increased VEGF secretion (ELISA) and invasive capacity (Transwell assay), but no synergistic effects were observed after the coadministration of ISO + T4. T3 reduced tumor growth and prevented the overexpression of ISO-stimulated factors through a pCREB-independent mechanism. ISO alone reduced tumor growth but increased tumor expression of cAMP response element (CRE)-dependent genes (real-time polymerase chain reaction, chromogranin A, neuron-specific enolase, survivin, vascular endothelial growth factor, urokinase plasmin activator and metalloproteinase-9 ) and some proteins related to NE differentiation and/or invasiveness (synaptophysin, VEGF, pCREB). Nude mice were inoculated with LNCaP cells and were treated for 6 wks with ISO (200 μg/d), triiodothyronine (T3, 2.5 μg/d) or both. We analyzed the effects of β-adrenergic stimulation (isoproterenol ) and/or thyroid hormone on neuroendocrine (NE) differentiation and cell invasion, using in vivo (LNCaP tumor) and in vitro models (LNCaP and DU145 human cells). ![]() ![]() ![]() It is well established that β-adrenergic activation (protein kinase A /cAMP response element binding protein ) promotes cancer progression, but the role of thyroid hormones is poorly understood. Prostate cancer cells are responsive to adrenergic and thyroid stimuli.
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