THE APURINIC APYRIMIDINIC ENDONUCLEASE (APE/REF-1) DNA-REPAIR ENZYME IS ELEVATED IN PREMALIGNANT AND MALIGNANT CERVICAL-CANCER/

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease (APE) is responsible for the repair of AP sites in DNA. In addition, t his enzyme has been shown to function as a redox factor facilitating t he DNA-binding capability of JUN and FOS HeLa AP-1, and numerous other transcription factors, including Myb, members of the CREB family and nuclear factor-kappa B. Although previously presumed to be ubiquitousl y expressed at comparable levels in all tissues and cell types, recent evidence has shown APE to vary significantly in its expression betwee n tissues and even within tissues. To further characterize APE express ion at various stages of cervical neoplasia, we investigated the level s of APE protein expression using immunohistochemistry in normal cervi x, pre-invasive and invasive squamous lesions of the cervix as well as in cervical cancer cell lines. We report here that the APE protein is predominantly expressed in the nuclei of cells from both primary tumo rs and cervical cell lines, but the level of APE protein is significan tly and dramatically elevated in cervical cancer tissue. These results implicate the use of anti-APE antibodies as an effective reagent in t he early detection of premalignant and malignant cancer of the cervix. These findings are suggestive that the increase of a DNA repair enzym e in cancerous cells may allow these cells to be refractive to chemoth erapy.