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ATM activation is accompanied with earlier stages of prostate tumorigenesis

Catherine Fan1, Rebecca Quan, Xinchang Feng

  • 1Department of Medicine, McMaster University, Hamilton, ON, Canada L8N 4A6.

Biochimica Et Biophysica Acta
|September 26, 2006
PubMed

Insights

Activation of ATM and Chk2 kinases in prostatic intraepithelial neoplasia (PIN) suggests they suppress early prostate cancer progression. Attenuated ATM activation may lead to carcinoma development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The ATM (ataxia telangiectasia mutated) kinase is crucial for maintaining genome integrity through DNA damage response pathways.
  • ATM activation, marked by ATM phosphorylation at serine 1981 (ATMpSer1981), initiates downstream signaling, including phosphorylation of H2AX (gammaH2AX), Chk2 (Chk2pThr68), and p53 (p53pSer15).

Purpose of the Study:

  • To investigate the role of the ATM pathway in prostate cancer development.
  • To analyze the activation status of ATM and its downstream targets in normal prostate glands, prostatic intraepithelial neoplasia (PIN), and prostate carcinoma.

Main Methods:

  • Immunohistochemistry (IHC) was used to assess the levels of ATMpSer1981, Chk2pThr68, gammaH2AX, and p53pSer15 in 35 primary prostate cancer specimens.
  • Analysis included normal glands, PIN lesions, and cancerous tissues.

Main Results:

  • Increased intensities and positive cell percentages for ATMpSer1981, Chk2pThr68, and gammaH2AX were observed in PINs compared to normal glands and carcinomas (p<0.001).
  • p53pSer15 showed no significant change in this pattern.
  • ATM and Chk2 kinases are specifically activated in PIN lesions, considered precursors to prostate cancer.

Conclusions:

  • ATM and Chk2 activation in early-stage prostate tumorigenesis (PINs) appears to suppress tumor progression.
  • A decrease or attenuation in ATM activation may correlate with the progression to prostate carcinoma.

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