RGD Reference Report - ATM activation is accompanied with earlier stages of prostate tumorigenesis. - Rat Genome Database

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ATM activation is accompanied with earlier stages of prostate tumorigenesis.

Authors: Fan, C  Quan, R  Feng, X  Gillis, A  He, L  Matsumoto, ED  Salama, S  Cutz, JC  Kapoor, A  Tang, D 
Citation: Fan C, etal., Biochim Biophys Acta. 2006 Oct;1763(10):1090-7. Epub 2006 Aug 24.
RGD ID: 2293869
Pubmed: PMID:16997395   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbamcr.2006.08.026   (Journal Full-text)

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 (gammaH2AX), 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, gammaH2AX, and p53pSer15 by immunohistochemistry (IHC) in normal glands, prostatic intraepithelial neoplasias (PINs), and carcinomas. Increases in the intensities of ATMpSer1981, Chk2pThr68, and gammaH2AX and in the percentage of cells that are positive for ATMpSer1981, Chk2pThr68, or gammaH2AX 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate carcinoma in situ  IEP 2293869protein:increased serine phosphorylation:prostate glandRGD 
prostate carcinoma in situ  ISOATM (Homo sapiens)2293869; 2293869protein:increased serine phosphorylation:prostate glandRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)


Additional Information