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Rad9 has a functional role in human prostate carcinogenesis

Aiping Zhu1, Charles Xia Zhang, Howard B Lieberman

  • 1Center for Radiological Research, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.

Cancer Research
|March 5, 2008
PubMed

Insights

Elevated Rad9 protein levels are common in prostate cancer, linked to aberrant methylation and gene amplification. Lowering Rad9 reduces tumor growth, suggesting its role as a biomarker and therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer is a leading cause of cancer death in men.
  • Cell cycle checkpoint proteins, like Rad9, are crucial for genome stability.
  • The role of Rad9 in prostate cancer pathogenesis requires investigation.

Purpose of the Study:

  • To investigate the relationship between Rad9 protein levels and prostate cancer.
  • To determine the mechanisms underlying elevated Rad9 expression in prostate cancer cells.
  • To evaluate Rad9 as a potential biomarker and therapeutic target for prostate cancer.

Main Methods:

  • Analysis of Rad9 protein levels in prostate cancer cell lines and human tumor samples.
  • Investigation of DNA methylation patterns in Rad9 intron 2 using 5'-aza-2'-deoxycytidine treatment.
  • Assessment of Rad9 gene copy number using Southern blot analysis.
  • Evaluation of Rad9's functional role by small interfering RNA-mediated knockdown and tumorigenicity assays in nude mice.

Main Results:

  • Four prostate cancer cell lines exhibited significantly higher Rad9 protein levels compared to normal prostate cells.
  • Hypermethylation of Rad9 intron 2 in DU145 cells and gene amplification in PC-3 cells were identified as mechanisms for elevated Rad9.
  • Rad9 knockdown reduced the tumorigenicity of prostate cancer cells in vivo.
  • High Rad9 protein levels were detected in a majority of human prostate tumor samples, correlating with advanced cancer stage.

Conclusions:

  • Aberrant DNA methylation and gene amplification contribute to elevated Rad9 protein levels in prostate cancer.
  • Rad9 plays an active role in prostate cancer development and progression.
  • Rad9 protein abundance serves as a promising biomarker for advanced prostate cancer and a potential target for novel diagnostic, prognostic, and therapeutic strategies.

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