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EGF Receptor Transactivation by α 1 ‐Adrenoceptors on Prostatic Hyperplastic Cells
Author(s) -
Silva Claudia Lucia M,
NascimentoViana Jessica B,
AlcántaraHernández Rocío,
GarcíaSáinz J Adolfo,
Noël François
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1266.7
Subject(s) - phenylephrine , transactivation , stromal cell , endocrinology , chemistry , cell growth , receptor , medicine , epidermal growth factor , biochemistry , gene expression , blood pressure , gene
Benign prostatic hyperplasia (BPH) is a progressive urological disorder related to an imbalance between cell proliferation and apoptosis. BPH is characterized by an increased number of epithelial, smooth muscle and stromal cells. Prostatic enlargement contributes to the lower urinary tract symptoms (LUTS/BPH). The participation of epidermal growth factor (EGF) receptor in G protein‐coupled receptor signaling is a process of transactivation critical for mitogenic activity in some models. Here we focused on the putative role of EGF receptor transactivation mediated by α 1D ‐adrenoceptors in stromal cell growth. Human BPH cells were treated with phenylephrine (3 μM) or vehicle (control) for either 15 min or 48h, and cell growth and protein expression were examined by Trypan Blue exclusion/MTT and Western blotting assays, respectively. Cell treatment with 3 μM phenylephrine (48h) induced a cell growth effect comparable to 0.1 μM EGF (166.3 ± 13.7 and 157.4 ± 14%, n = 5 experiments performed in quadruplicate, for phenylephrine and EGF, respectively, P < 0.001). The effect of phenylephrine was blocked by the α 1D ‐adrenoceptor antagonists BMY7378 (50 nM; 92.8 ± 4.7%, n = 5, P < 0.001), LDT3 (50 nM; 94.2 ± 8.2%, n = 5, P < 0.001) and LDT5 (50 nM; 92.6 ± 9.1%, n = 5, P < 0.001) suggesting that these receptors are involved in cell growth. Then we evaluated the downstream α 1D ‐adrenoceptor signaling. Phenylephrine (3 μM, 15 min) induced p‐ERK expression and the α 1D ‐adrenoceptor antagonists also blocked this effect (n = 4). Furthermore, the phenylephrine‐induced cell growth was blocked by the metalloproteinase inhibitor GM6001 (10 μM), the selective EGF receptor inhibitor AG1478 (5 μM) and MEK inhibitor PD98059 (1 μM). In conclusion, these results suggest that EGF receptor transactivation by α 1D ‐adrenoceptor is relevant for human stromal cell proliferation and may contribute to prostatic enlargement and LUTS/BPH. Support or Funding Information CNPq, Brazil [455436/2014‐2]