RGD Reference Report - Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. - Rat Genome Database

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Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer.

Authors: Kelley, MR  Cheng, L  Foster, R  Tritt, R  Jiang, J  Broshears, J  Koch, M 
Citation: Kelley MR, etal., Clin Cancer Res. 2001 Apr;7(4):824-30.
RGD ID: 2315666
Pubmed: PMID:11309329   (View Abstract at PubMed)

The DNA base excision repair pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial step in the BER pathway involves the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not only as an AP endonuclease but also as a redox-modifying factor for a variety of transcription factors including Fos, Jun, paired box containing genes (PAX), nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels, scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and 67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1 nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and 36%, respectively) compared with BPH (5%). There was no correlation with prostate-specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer, the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm of PIN and cancer compared with BPH. Given these results, we conclude that Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role, through its repair, redox, or both functions, in the physiology of the early development of prostate cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate carcinoma in situ  IEP 2315666protein:increased expression more ...RGD 
prostate carcinoma in situ  ISOAPEX1 (Homo sapiens)2315666; 2315666protein:increased expression more ...RGD 
Prostatic Neoplasms  IEP 2315666protein:increased expression more ...RGD 
Prostatic Neoplasms  ISOAPEX1 (Homo sapiens)2315666; 2315666protein:increased expression more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apex1  (apurinic/apyrimidinic endodeoxyribonuclease 1)

Genes (Mus musculus)
Apex1  (apurinic/apyrimidinic endonuclease 1)

Genes (Homo sapiens)
APEX1  (apurinic/apyrimidinic endodeoxyribonuclease 1)


Additional Information