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Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer

Jason P W Carey1, Ananthi J Asirvatham, Oliver Galm

  • 1Department of Biology, Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, USA. j_carey84@msn.com

BMC Cancer
|June 9, 2009
PubMed
Abstract

Insights

Inhibitor of differentiation 4 (Id4) functions as a tumor suppressor in prostate cancer, with its down-regulation linked to promoter hypermethylation. Restoring Id4 expression inhibits cancer cell proliferation and increases apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Inhibitor of differentiation 4 (Id4) is a dominant-negative regulator of basic helix loop helix (bHLH) transcription factors.
  • Loss of Id4 expression, associated with promoter hypermethylation in many cancers, suggests a tumor suppressor role.
  • This study provides functional evidence for Id4's tumor suppressor activity and its role in cancer-associated epigenetic reprogramming.

Purpose of the Study:

  • To investigate the role of Id4 as a tumor suppressor in prostate cancer.
  • To elucidate the molecular mechanisms underlying Id4 dysregulation in prostate cancer cells.

Main Methods:

  • Data mining to assess Id4 expression in prostate cancer.
  • Methylation-specific polymerase chain reaction (MSP) to analyze Id4 promoter methylation.
  • Functional assays including cell cycle analysis, RT-PCR, real-time PCR, western blot, and immunocytochemistry to evaluate the effects of ectopic Id4 expression.

Main Results:

  • Id4 expression is significantly down-regulated in prostate cancer, particularly in the DU145 cell line, due to promoter hypermethylation.
  • Ectopic Id4 expression in DU145 cells induced apoptosis, decreased cell proliferation via S-phase arrest, and increased expression of p53, p21, p27, and androgen receptor.
  • Ectopic Id4 expression in PC3 cells also led to prolonged G2/M phase arrest.

Conclusions:

  • Id4 functions as a direct tumor suppressor in prostate cancer.
  • Id4 influences multiple cellular processes, including cell proliferation and morphology, potentially by reactivating silenced tumor suppressors.
  • Epigenetic silencing of Id4 contributes to prostate cancer development.

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