The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)828-837
Number of pages10
JournalJournal of Cellular Biochemistry
Volume109
Issue number4
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Core Binding Factor Alpha 1 Subunit
Cell growth
Androgens
Tumors
Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Cells
Dihydrotestosterone
Growth
Neoplasms
Bone
Cyclin-Dependent Kinases
Androgen Receptors
Prostate
Steroid hormones
Cyclins
Osteoblasts
Transcription
Luciferases
Bone and Bones

Keywords

  • Bone
  • Cell cycle
  • Cell signaling
  • Proliferation
  • Steroid hormone receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Van Der Deen, M., Akech, J., Wang, T., FitzGerald, T. J., Altieri, D. C., Languino, L. R., ... Stein, G. S. (2010). The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells. Journal of Cellular Biochemistry, 109(4), 828-837. https://doi.org/10.1002/jcb.22463

The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells. / 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.

In: Journal of Cellular Biochemistry, Vol. 109, No. 4, 01.03.2010, p. 828-837.

Research output: Contribution to journalArticle

Van Der Deen, M, Akech, J, Wang, T, FitzGerald, TJ, Altieri, DC, Languino, LR, Lian, JB, van Wijnen, AJ, Stein, JL & Stein, GS 2010, 'The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells', Journal of Cellular Biochemistry, vol. 109, no. 4, pp. 828-837. https://doi.org/10.1002/jcb.22463
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. / The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells. In: Journal of Cellular Biochemistry. 2010 ; Vol. 109, No. 4. pp. 828-837.
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