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Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression.

AbstractPURPOSE:
Id proteins are dominant-negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of Id-1 and Id-2 proteins as molecular makers for prostate cancer progression.
EXPERIMENTAL DESIGN:
Using the technique of immunohistochemistry, we determined Id-1 and Id-2 expression in a panel of 67 human prostate biopsies. We also manipulated Id-1 and Id-2 expression in LNCaP and PC3 prostate cancer cell lines and determined the effects on invasion in vitro, matrix metalloproteinase secretion, and proliferation.
RESULTS:
Both Id-1 and Id-2 proteins were up-regulated during human prostate cancer progression in vivo and were overexpressed in highly aggressive prostate cancer cells. In vitro, constitutive expression of Id-1, and to a lesser extent Id-2, converted nonaggressive LNCaP prostate cancer cells into more proliferative and invasive cells and increased their secretion of matrix metalloproteinases. Conversely, the down-regulation of Id-2 expression in highly metastatic PC3 cells reduced their growth potential and invasiveness.
CONCLUSIONS:
We propose that both Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer.
AuthorsJean-Philippe Coppe, Yoko Itahana, Dan H Moore, James L Bennington, Pierre-Yves Desprez
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 6 Pg. 2044-51 (Mar 15 2004) ISSN: 1078-0432 [Print] United States
PMID15041724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • ID1 protein, human
  • ID2 protein, human
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Protein 2
  • Repressor Proteins
  • Transcription Factors
Topics
  • Biomarkers, Tumor (analysis, genetics)
  • Cell Line, Tumor
  • DNA-Binding Proteins (analysis, genetics)
  • Disease Progression
  • Helix-Loop-Helix Motifs
  • Humans
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Protein 2
  • Male
  • Neoplasm Invasiveness
  • Prostatic Neoplasms (genetics, pathology)
  • Repressor Proteins (analysis, genetics)
  • Transcription Factors (analysis, genetics)

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