Accession Number:
AD1006257
Title:
Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer
Descriptive Note:
Technical Report,30 Sep 2012,29 Sep 2015
Corporate Author:
University of Southern California Los Angeles United States
Personal Author(s):
Report Date:
2015-12-01
Pagination or Media Count:
105.0
Abstract:
The purpose of this project is to investigate the key roles of the monoamine oxidase A MAO A enzyme in the progression and metastasis of prostate cancer PCa. During this funding period, we delineated the functional and mechanistic roles of MAO A in promoting tumor metastasis, determined MAO A functions in PCa by defining its roles in reactive oxygen species production and augmentation of HIF1-mediated signaling, and developed a MHI clorgyline, a novel pharmacological inhibitor of MAO A for targeted therapy and noninvasive imaging of PCa. Throughout the Year 3, we investigated the effect of hypoxia on MAO A and found that hypoxia induces MAO A expression and activity. We assessed the tumor-targeting properties of NIR-clorgyline for PCa in vivo and demonstrated its tumor-specificity in mouse xenograft model through NIR near infrared imaging. We generated MAO APten double KO mice and showed that deletion of MAO A delays PCa development and facilitates an immunostimulatory environment in the Pten KO mouse model of prostate adenocarcinoma.