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Inhibition of IGF-1 signaling by genistein: modulation of E-cadherin expression and downregulation of β-catenin signaling in hormone refractory PC-3 prostate cancer cells

Authors
 Joomin Lee  ;  Jihyeung Ju  ;  Seyeon Park  ;  Sung Joon Hong  ;  Sun Yoon 
Citation
 NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, Vol.64(1) : 153-162, 2012 
Journal Title
 NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 
ISSN
 0163-5581 
Issue Date
2012
MeSH
Cadherins/metabolism* ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Genistein/pharmacology* ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Insulin-Like Growth Factor I/metabolism* ; Insulin-Like Growth Factor I/pharmacology ; Male ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation/drug effects ; Prostatic Neoplasms/drug therapy* ; Prostatic Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Receptor, IGF Type 1/metabolism ; Signal Transduction/drug effects ; Tyrosine/metabolism ; beta Catenin/metabolism*
Keywords
Cadherins/metabolism* ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Genistein/pharmacology* ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Insulin-Like Growth Factor I/metabolism* ; Insulin-Like Growth Factor I/pharmacology ; Male ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation/drug effects ; Prostatic Neoplasms/drug therapy* ; Prostatic Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Receptor, IGF Type 1/metabolism ; Signal Transduction/drug effects ; Tyrosine/metabolism ; beta Catenin/metabolism*
Abstract
Elevated levels of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of several different cancers, including prostate cancer. Inhibition of IGF-1 and the downstream signaling pathways mediated by the activation of the IGF-1 receptor (IGF-1R) may be involved in inhibiting prostate carcinogenesis. We investigated whether genistein downregulated the IGF-1/IGF-1R signaling pathway and inhibited cell growth in hormone refractory PC-3 prostate cancer cells. Genistein treatment caused a significant inhibition of IGF-1-stimulated cell growth. Flow cytometry analysis revealed that genistein significantly decreased the number of IGF-1-stimulated cells in the G0/G1 phase of the cell cycle. In IGF-1-treated cells, genistein effectively inhibited the phosphorylation of IGF-1R and the phosphorylation of its downstream targets, such as Src, Akt, and glycogen synthase kinase-3β (GSk-3β). IGF-1 treatment decreased the levels of E-cadherin but increased the levels of β-catenin and cyclin D1. However, genistein treatment greatly attenuated IGF-1-induced β-catenin signaling that correlated with increasing the levels of E-cadherin and decreasing cyclin D1 levels in PC-3 cells. In addition, genistein inhibited T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity. These results showed that genistein effectively inhibited cell growth in IGF-1-stimulated PC-3 cells, possibly by inhibiting downstream of IGF-1R activation.
Full Text
http://www.tandfonline.com/doi/abs/10.1080/01635581.2012.630161
DOI
22098108
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Lee, Joo Min(이주민)
Hong, Sung Joon(홍성준) ORCID logo https://orcid.org/0000-0001-9869-065X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91574
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