Pro-oxidant enzyme Nox-1 over expression in TRAMP prostate cancer murine model reflects clinical findings

Abstract

1970

Nox-1 is a membrane-bound NADPH oxidase that generates superoxide anion. We have previously reported that 80% of human prostate cancers exhibit cancer-specific over expression of both Nox-1 mRNA and protein (2004). Furthermore, we have demonstrated that experimental over expression on Nox-1 in the DU-145 prostate cancer cell line markedly increases reactive oxygen species (ROS), angiogenesis and tumor growth (2001). Others have shown that antioxidants block prostate cancer in SV-40 transgenic mice (2004). We therefore evaluated the TRAMP mouse model of prostate cancer for Nox-1 expression in order to identify an appropriate model for this molecular alteration observed so commonly in human prostate cancer. At 10 weeks of age TRAMP mice and wild type mice have the same level of Nox-1 mRNA expression, however by 18 weeks, half of the mice demonstrate increased Nox-1 expression in the prostate despite a normal appearing gland. By 25-30 weeks, approximately 70% of TRAMP prostates express increased levels of Nox-1 message using quantitative RT-PCR. Other Nox isoforms, including Nox-4 show no consistent difference in wild type and transgenic prostates. The TRAMP model of murine prostate cancer may therefore be an appropriate model system to evaluate the role Nox-1 over expression plays in prostate carcinogenesis. Because the transgenic prostates initially express normal levels of Nox-1 this may be an appropriate model to study Nox-1 transcription regulation, a control point particularly relevant to human tumors.