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The cancer‐related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells
Author(s) -
van der Deen Margaretha,
Akech Jacqueline,
Wang Tao,
FitzGerald Thomas J.,
Altieri Dario C.,
Languino Lucia R.,
Lian Jane B.,
van Wijnen Andre J.,
Stein Janet L.,
Stein Gary S.
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22463
Subject(s) - lncap , prostate cancer , cancer research , runx2 , biology , dihydrotestosterone , cell growth , cyclin dependent kinase , transforming growth factor beta , transforming growth factor , androgen receptor , endocrinology , transcription factor , medicine , chemistry , cell cycle , cancer , androgen , hormone , biochemistry , gene , genetics
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 5α‐dihydrotestosterone (DHT) or tumor growth factor β (TGFβ) 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 TGFβ or DHT signaling modulates the transcriptional activity of Runx2 and vice versa, we performed luciferase reporter assays. In PC3 cells that express TGFβRII, TGFβ 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 TGFβ and androgen responsive pathways that support prostate cancer cell growth. J. Cell. Biochem. 109: 828–837, 2010. © 2010 Wiley‐Liss, Inc.