Heme Oxygenase 1 (HO-1): a novel proten in prostate cancer cell proliferation, migration and invasion

GUERON GERALDINE; FERRANDO MERCEDES; DE LUCA PAOLA; DE SIERVI ADRIANA; NAVONE NORA; VAZQUEZ ELBA

San Diego, California, USA

Congreso; Annual Meeting American Association for Cancer Research; 2008

American Association for Cancer Research

Prostate cancer (PCa) is considered the third leading cause of cancer death among men. However because of the complexity of this disease, PCa target genes have been difficult to identify. Recently it has been recognized that inflammation collaborates with PCa tumorigenesis. Heme oxygenases are the rate-limiting enzymes in heme degradation. Human heme oxygenase 1 (HO-1) is induced during hypoxia, ischemia/reperfusion, and inflammation. It is becoming more apparent that HO-1 activity not only provides protection in oxidative injury, but is also involved in direct modulation of the infiltrating inflammatory cells. To assess HO-1 role in PCa, we first study HO-1 protein expression levels in different PCa cell lines. Androgen independent cells (PC3) showed very low basal levels in comparison with androgen sensitive cell lines (MDA PCa2b and LNCaP). Moreover, hemin (70 µM, 24h), a known HO-1 inducer, increased HO-1 protein and mRNA expression levels in those cell lines. Accordingly, HO-1 promoter activity was increased by hemin and ARE (anti-oxidant response element) mutation sites totally abolished this induction in PCa cell lines. Furthermore, treatment of PCa cell cultures with hemin resulted in a 23% and 45% (p