Document Detail

The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFbeta in prostate cancer cells.
MedLine Citation:
PMID:  20082326     Owner:  NLM     Status:  MEDLINE    
Prostate cancer cells often metastasize to bone where osteolytic lesions are formed. Runx2 is an essential transcription factor for bone formation and suppresses cell growth in normal osteoblasts but may function as an oncogenic factor in solid tumors (e.g., breast, prostate). Here, we addressed whether Runx2 is linked to steroid hormone and growth factor signaling, which controls prostate cancer cell growth. Protein expression profiling of prostate cell lines (i.e., PC3, LNCaP, RWPE) treated with 5alpha-dihydrotestosterone (DHT) or tumor growth factor beta (TGFbeta) revealed modulations in selected cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors that are generally consistent with mitogenic responses. Endogenous elevation of Runx2 and diminished p57 protein levels in PC3 cells are associated with faster proliferation in vitro and development of larger tumors upon xenografting these cells in bone in vivo. To examine whether TGFbeta or DHT signaling modulates the transcriptional activity of Runx2 and vice versa, we performed luciferase reporter assays. In PC3 cells that express TGFbetaRII, TGFbeta and Runx2 synergize to increase transcription of synthetic promoters. In LNCaP cells that are DHT responsive, Runx2 stimulates the androgen receptor (AR) responsive expression of the prostate-specific marker PSA, perhaps facilitated by formation of a complex with AR. Our data suggest that Runx2 is mechanistically linked to TGFbeta and androgen responsive pathways that support prostate cancer cell growth.
Margaretha van der Deen; Jacqueline Akech; Tao Wang; Thomas J FitzGerald; Dario C Altieri; Lucia R Languino; Jane B Lian; Andre J van Wijnen; Janet L Stein; Gary S Stein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  109     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-08-12     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  828-37     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
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MeSH Terms
Androgens / pharmacology*
Cell Line, Tumor
Cell Proliferation*
Core Binding Factor Alpha 1 Subunit / physiology*
Dihydrotestosterone / pharmacology
Gene Expression Regulation, Neoplastic
Neoplasm Proteins / analysis
Prostatic Neoplasms / pathology*
Transforming Growth Factor beta / pharmacology*
Grant Support
AR048818/AR/NIAMS NIH HHS; CA078810/CA/NCI NIH HHS; CA082834/CA/NCI NIH HHS; CA090917/CA/NCI NIH HHS; DK032520/DK/NIDDK NIH HHS; HL054131/HL/NHLBI NIH HHS; P01 AR048818/AR/NIAMS NIH HHS; P01 AR048818-09/AR/NIAMS NIH HHS; P01 AR048818-10/AR/NIAMS NIH HHS; P01 CA082834/CA/NCI NIH HHS; P01 CA082834-10/CA/NCI NIH HHS; P01 CA082834-11/CA/NCI NIH HHS; R01 AR039588/AR/NIAMS NIH HHS; R01 AR049069/AR/NIAMS NIH HHS; R01 CA078810/CA/NCI NIH HHS; R01 CA078810-13/CA/NCI NIH HHS; R01 CA078810-14/CA/NCI NIH HHS; R01 CA090917/CA/NCI NIH HHS; R01 CA090917-10/CA/NCI NIH HHS; R01 CA109874/CA/NCI NIH HHS; R01 CA109874-05/CA/NCI NIH HHS; R01 CA109874-06/CA/NCI NIH HHS; R01 HL054131/HL/NHLBI NIH HHS; R01 HL054131-09/HL/NHLBI NIH HHS; R01 HL054131-10/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Androgens; 0/Core Binding Factor Alpha 1 Subunit; 0/Neoplasm Proteins; 0/Transforming Growth Factor beta; 08J2K08A3Y/Dihydrotestosterone

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