Bone morphogenetic protein-2 blocks MDA MB 231 human breast cancer cell proliferation by inhibiting cyclin-dependent kinase-mediated retinoblastoma protein phosphorylation

Nandini Ghosh-Choudhury, Kathleen Woodruff, Wenbo Qi, Anthony Celeste, Sherry L. Abboud, Goutam Ghosh Choudhury

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Bone morphogenetic protein-2 (BMP-2) has been shown to act as an antiproliferative agent for a number of different cell types. We show that BMP-2 dose-dependently inhibits growth of MDA MB 231 human breast cancer cells. Epidermal growth factor (EGF) stimulates DNA synthesis and entry of these cells into the S-phase. BMP-2 inhibits EGF-induced DNA synthesis by arresting them in G1 phase of the cell cycle. BMP-2 increases the level of cyclin kinase inhibitor p21. Furthermore, we show that exposure of MDA MB 231 cells to BMP-2 stimulates association of p21 with cyclin D1 and with cyclin E resulting in the inhibition of their associated kinase activities. Finally, BMP-2 treatment is found to cause hypophosphorylation of the retinoblastoma protein (pRb), a key regulator of cell cycle progression. Our data provide a mechanism for the antiproliferative effect of BMP-2 in the breast cancer cells. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)705-711
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume272
Issue number3
DOIs
Publication statusPublished - Jun 16 2000

    Fingerprint

Keywords

  • BMP-2
  • Breast cancer cells
  • p21
  • pRb

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this