ATM activation is accompanied with earlier stages of prostate tumorigenesis

作者：Fan Catherine; Quan Rebecca; Feng Xinchang; Gillis Aubrey; He Lizhi; Matsumoto Edward D; Salama Sam; Cutz Jean Claude; Kapoor Anil^*; Tang Damu

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2006, 1763(10): 1090-1097.

DOI：10.1016/j.bbamcr.2006.08.026

• ATM
• Chk2
• p53
• gamma H2AX
• prostate tumorigenesis

The ATM (ataxia telangiectasia mutated) kinase plays an essential role in maintaining genome integrity by coordinating cell cycle arrest, apoptosis, and DNA damage repair. Phosphorylation of ATM at serine 1981 (ATMpSer1981) by DNA damage activates ATM, which subsequently phosphorylates H2AX Ser139 (gamma H2AX), Chk2 Thr68 (Chk2pThr68), and p53 Ser15 (p53pSer15). To determine the role of the ATM pathway in prostate cancer tumorigenesis, we have analyzed 35 primary prostate cancer specimens for ATMpSer1981 (ATM activation), Chk2pThr68, gamma H2AX, and p53pSer15 by immunohistochemistry (IHC) in normal glands, prostatic intraepithelial neoplasias (PINs), and carcinomas. Increases in the intensities of ATMpSer1981, Chk2pThr68, and gamma H2AX and in the percentage of cells that are positive for ATMpSer1981, Chk2pThr68, or gamma H2AX were observed in PINs (p < 0.001) compared to normal prostatic glands and carcinoma. However, this pattern of immunostaining was not seen for p53pSer15. Thus, ATM and Chk2 are specifically activated in PINs. As PINs are generally regarded as precursors of prostatic carcinoma, our results suggest that ATM and Chk2 activation at earlier stages of prostate tumorigenesis suppresses tumor progression, with attenuation of ATM activation leading to cancer progression.

• 出版日期2006-10