Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7

J Cancer Res Clin Oncol. 2000 May;126(5):271-9. doi: 10.1007/s004320050342.

Abstract

Bone morphogenetic proteins (BMPs) are involved in the development of various organs including the mammary gland. They are well-regulated and act in a time-, concentration- and cell-type-specific manner. We found that BMP-2 is expressed in primary breast tumor tissue samples and in breast cancer cell lines. Hybridization of labeled cDNA, obtained from the breast cancer cell line MCF-7, against the Atlas human cDNA expression array revealed differential gene expression depending on BMP-2 treatment. The most prominent changes were observed for the helix-loop-helix proteins Id-1, Id-2 and Id-3. Id-1 expression had increased severalfold after 4 h and was even higher after 24 h. Id-2 and Id-3 were more strongly induced after 4 h and showed no further significant change after 24 h. Analysis of cell-cycle distribution revealed a marked increase of the sub-G1 phase after 48 h in serum-deprived cells. In the presence of BMP-2 no change was observed over 48 h indicating that BMP-2 does not induce apoptosis. In addition, expression of caspase-3 was reduced in BMP-2-treated cells after 24 h. In summary, our results clearly indicate that BMP-2 is a susceptibility factor keeping the cells ready for the integration of various other signals for cell progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology*
  • Bone Morphogenetic Proteins / physiology
  • Breast / metabolism*
  • Breast / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Caspase 3
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • DNA Primers
  • Female
  • Gene Expression Regulation, Neoplastic
  • Helix-Loop-Helix Motifs / drug effects
  • Helix-Loop-Helix Motifs / genetics
  • Humans
  • Image Processing, Computer-Assisted
  • Inhibitor of Differentiation Protein 1
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism*
  • Neoplasms, Hormone-Dependent / pathology
  • Repressor Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / drug effects*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • DNA Primers
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • Repressor Proteins
  • Transcription Factors
  • Transforming Growth Factor beta
  • CASP3 protein, human
  • Caspase 3
  • Caspases