| EGFR ligand switch in late stage prostate cancer contributes to changes in cell signaling and bone remodeling. | |
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MedLine Citation:
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PMID: 19143022 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Bone metastasis occurs frequently in advanced prostate cancer (PCa) patients; however, it is not known why this happens. The epidermal growth factor receptor (EGFR) ligand EGF is available to early stage PCa; whereas, TGF-alpha is available when PCa metastasizes. Since the microenvironment of metastases has been shown to play a role in the survival of the tumor, we examined whether the ligands had effects on cell survival and proliferation in early and late PCa. METHODS: We used LNCaP cells as a model of early stage, non-metastatic PCa and the isogenic C4-2B cells as a model of late stage, metastatic PCa. RESULTS: We found that the proliferation factor MAPK and the survival factor AKT were differentially activated in the presence of different ligands. TGF-alpha induced growth of C4-2B cells and not of the parental LNCaP cells; however, LNCaP cells expressing a constitutively active AKT did proliferate with TGF-alpha. Therefore, AKT appeared to be the TGF-alpha-responsive factor for survival of the late stage PCa cells. LNCaP cells exposed to EGF produced more osteoprotegerin (OPG), an inhibitor of bone remodeling, than C4-2B cells with TGF-alpha, which had increased expression of RANKL, an activator of bone remodeling. In concordance, TGF-alpha-treated C4-2B conditioned medium was able to differentiate an osteoclast precursor line to a greater extent than EGF-treated C4-2B or TGF-alpha-treated LNCaP conditioned media. CONCLUSION: The switch in EGFR ligand availability as PCa progresses affects cell survival and contributes to bone remodeling. |
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Authors:
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Alyse M DeHaan; Natalie M Wolters; Evan T Keller; Kathleen M Woods Ignatoski |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Prostate Volume: 69 ISSN: 1097-0045 ISO Abbreviation: Prostate Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-02-25 Completed Date: 2009-03-13 Revised Date: 2011-05-04 |
Medline Journal Info:
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Nlm Unique ID: 8101368 Medline TA: Prostate Country: United States |
Other Details:
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Languages: eng Pagination: 528-37 Citation Subset: IM |
Copyright Information:
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(c) 2009 Wiley-Liss, Inc. |
Affiliation:
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Department of Urology, University of Michigan Health System, Ann Arbor, Michigan 48109-0654, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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metabolism*,
pathology Bone Neoplasms / metabolism*, secondary Bone Remodeling / drug effects, physiology* Cell Line, Tumor Disease Progression Epidermal Growth Factor / pharmacology Humans Ligands Male Mitogen-Activated Protein Kinase Kinases / metabolism Models, Biological Neoplasm Staging Prostatic Neoplasms / metabolism*, pathology Proto-Oncogene Proteins c-akt / metabolism RANK Ligand Receptor, Epidermal Growth Factor / metabolism* Signal Transduction / drug effects, physiology* Transforming Growth Factor alpha / metabolism, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA093900/CA/NCI NIH HHS; R01 CA098513-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/RANK Ligand; 0/TNFSF11 protein, human; 0/Transforming Growth Factor alpha; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
| Comments/Corrections | |
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