Many previous studies have suggested that inflammation may be a causative process in prostatic carcinogenesis. As such, the histological classification of Proliferative Inflammatory Atrophy (PIA) has been hypothesized to be a precursor lesion to prostatic intraepithelial neoplasias (PIN) and early adenocarcinomas. In a recently initiated project, we propose to test this hypothesis by directly expressing pro-inflammatory cytokines, as well as their activated signal transducing molecules, in the prostate and assessing the effect on prostatic oncogenesis. In collaboration with Bill Farrar and Lionel Feigenbaum, we have generated transgenic mice that bear a transgene carrying the IL-6 gene downstream from a LoxP-flanked stop signal. These transgenic mice were crossed to mice bearing a prostate-specific CRE recombinase gene, thereby inducing IL-6 expression in the prostate. Similarly, we are generating interferon-g and activated STAT-3 transgenic lines. These mice will be initially studied for signs of inflammation and tumor formation by histopathology and for molecular signatures of transformation by Bill Farrar's laboratory. Our initial studies are now characterizing IL-6 and IFN-g expression in the trangenic founders crossed onto the CRE background. These mice may prove valuable for studying the ability of anti-inflammatory drugs to inhibit or alter tumor formation.
NIH ExPorter
NIH ExPorter