title: Androgen receptor inhibits epithelial-mesenchymal transition, migration, and invasion of PC-3 prostate cancer cells.
abstract: Bone metastasis is very common in prostate cancer (PCa) and causes severe pain. PC-3 is an androgen receptor (AR)-negative PCa cell line with high metastatic potential established from PCa bone metastasis. We observed that re-expression of AR, which is located in the cytoplasm in the absence of androgen, suppressed cell motility, migration, and invasion of PC-3 cells as determined by wound healing assay and transwell assay. Micro-Western Array and Western blotting analysis indicated that re-expression of AR increased APC, Akt2, Akt3, PI3K p85, phospho-PI3K p85 Tyr458, PI3K p85, and E-cadherin but decreased GSK-3β, phospho-GSK-3β Ser9, phospho-mTOR Ser2448, Skp2, NF-κB p50, Slug, N-cadherin, β-catenin, vimentin, MMP-9, and Snail. Migration and invasion of PC-3 and PC-3(AR) cells were promoted by EGF or IGF-1 but were suppressed by Casodex. Re-expression of AR reduced the activity of MMP-2 and MMP-9 in PC-3 cells. Our observations suggested that re-expressing AR suppresses migration and invasion of PC-3 cells via regulation of EMT marker proteins and MMP activity.
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; Department of Life Sciences, National Central University, Taoyuan County 32001, Taiwan.
authors: Chieh
authors: C
authors: Huo
authors: Department of Life Sciences, National Central University, Taoyuan County 32001, Taiwan.
authors: Yung-Hsi
authors: YH
authors: Kao
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Graduate Program for Aging, China Medical University, Taichung, Taiwan; Biotechnology Center, National Chung Hsing University, Taichung, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. Electronic address: cpchuu@nhri.org.tw.
authors: Chih-Pin
authors: CP
authors: Chuu
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology*
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; C053541:bicalutamide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Androgen receptor; Epithelial–mesenchymal transition; Invasion; Migration; PC-3; Prostate cancer