Down-regulation of Id-1 expression is associated with TGF beta 1-induced growth arrest in prostate epithelial cells

Biochim Biophys Acta. 2002 Apr 15;1570(3):145-52. doi: 10.1016/s0304-4165(02)00189-7.

Abstract

Transforming growth factor beta1 (TGF beta 1) plays important roles in the regulation of cell growth and differentiation in both normal and malignant prostate epithelial cells. Although certain pathways have been suggested, the mechanisms responsible for the action of TGF beta 1 are not well understood. In the present study, using a human papilloma virus 16 E6/E7 immortalized prostate epithelial cell line, HPr-1, we report that TGF beta 1 was able to suppress the expression of Id-1, a helix-loop-helix (HLH) protein, which plays important roles in the inhibition of cell differentiation and growth arrest. In addition, a decrease at both Id-1 mRNA and protein expression levels was associated with TGF beta 1-induced growth arrest and differentiation, indicating that Id-1 may be involved in TGF beta 1 signaling pathway. The fact that up-regulation of p21(WAF1), one of the downstream effectors of Id-1, was observed after exposure to TGF beta 1 further indicates the involvement of Id-1 in the TGF beta 1-induced growth arrest in HPr-1 cells. However, increased expression of p27(KIP1) was also observed in the TGF beta 1-treated cells, suggesting that in addition to down-regulation of Id-1, other factors may be involved in the TGF beta 1-induced cell growth arrest and differentiation in prostate epithelial cells. Our results provide evidence for the first time that TGF beta 1 may be one of the upstream regulators of Id-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Cycle Proteins / biosynthesis
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / biosynthesis
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / physiology
  • Down-Regulation*
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Helix-Loop-Helix Motifs / physiology*
  • Humans
  • Inhibitor of Differentiation Protein 1
  • Male
  • Prostate / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism
  • Repressor Proteins*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / physiology
  • Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins / biosynthesis
  • Up-Regulation

Substances

  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Repressor Proteins
  • TGFB1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27