Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells

  • Authors:
    • Kentaro Tomari
    • Toru Kumagai
    • Takahisa Shimizu
    • Ken Takeda
  • View Affiliations

  • Published online on: February 1, 2005     https://doi.org/10.3892/ijmm.15.2.253
  • Pages: 253-258
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Abstract

Bone morphogenetic protein-2 (BMP-2), a multifunctional member of the transforming growth factor (TGF)-β, superfamily, has powerful osteoinductive effects and causes cell cycle arrest in a variety of transformed cell lines. We have observed BMP-2-induced inhibition of cell proliferation in an androgen-dependent human prostate cancer cell line (LNCaP). To investigate the mechanism of inhibition of androgen-dependent growth by BMP-2, we examined the effect of dihydrotestosterone (DHT) and/or BMP-2 on cell cycle-related proteins in LNCaP cells. BMP-2 decreased the phosphorylation of retinoblastoma (Rb) protein induced by treatment with DHT. DHT-induced expression of cyclin A and cyclin-dependent kinase 2 (CDK2) protein was also inhibited by co-treatment with BMP-2. Furthermore, BMP-2 induced expression of p21WAF1/CIP1, a CDK inhibitor. These results indicate that changes in expression of these proteins lead to modulation of the phosphorylation state of Rb. DHT-induced E2F-1 protein and mRNA expressions was also inhibited by BMP-2, suggesting that BMP-2 inhibits DHT-induced growth of LNCaP cells through a decrease in E2F protein expression and suppression of E2F activity by hypophosphorylation of Rb.

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February 2005
Volume 15 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tomari K, Kumagai T, Shimizu T and Takeda K: Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells. Int J Mol Med 15: 253-258, 2005
APA
Tomari, K., Kumagai, T., Shimizu, T., & Takeda, K. (2005). Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells. International Journal of Molecular Medicine, 15, 253-258. https://doi.org/10.3892/ijmm.15.2.253
MLA
Tomari, K., Kumagai, T., Shimizu, T., Takeda, K."Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells". International Journal of Molecular Medicine 15.2 (2005): 253-258.
Chicago
Tomari, K., Kumagai, T., Shimizu, T., Takeda, K."Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells". International Journal of Molecular Medicine 15, no. 2 (2005): 253-258. https://doi.org/10.3892/ijmm.15.2.253