IMPLICATIONS OF HEME-OXYGENASE 1 MODULATION OF INTERFERON INDUCIBLE ANTIVIRAL (MX1) IN PROSTATE CANCER

EMILIANO ORTIZ,; ALEJANDRA PAEZ,; NICOLAS ANSELMINO; JAVIER COTIGNOLA; MARIA PIA VALACCO; ELBA VAZQUEZ.; GUERON GERALDINE

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

The principal goal currently within prostate cancer (PCa) researchis to unveil markers for early detection of aggressive tumors thatare predestined to invade and metastasize. We have previously reportedthat heme oxygenase-1 (HO-1) exerts an anti-tumoral rolein PCa, ascertaining it as a logical target for therapy intervention.HO-1 over-expression impairs tumor growth and angiogenesis invivo. Considering the cross talk between inflammation, angiogenesisand cancer progression, our next step sought to identify signalingpathways by which HO-1 could be operating. Towards this end weperformed and analysed RNAseq data on PCa cells overexpressingHO-1 pharmacologically or genetically. Of note HO-1 significantlyup-regulated the human myxovirus resistant protein A (Mx1). In vitrostudies revealed that forced expression of HO-1 in PCa cells, significantlyup-regulated MX1 mRNA and protein levels and shifted itslocalization towards the perinuclear area.To address the relevance of MX1 in PCa we searched the publiccancer microarray database, Oncomine. MX1 was ranked by itsP-value for every analysis scoring a gene rank. We then obtained amedian rank (Median P-value rank across datasets) for MX1. Theexpression profile for MX1 showed a significant down-regulation(fold change 1.5, P