Poster Presentation 27th Lorne Cancer Conference 2015

A ROLE FOR E6AP IN THE REGULATION OF p27 IN PROSTATE CANCER DEVELOPMENT AND PROGRESSION. (#246)

Dinesh Raghu 1 2 , Piotr Paul 1 2 , Ai-Leen Chan 1 , Luke Lambeth 1 , Cristina Gamell 1 , Elena Takano 1 , Siddhartha Deb 1 , Stephen Fox 1 , Sue Haupt 1 , Ygal Haupt 1
  1. Peter MacCallum Cancer centre, East Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia

Prostate cancer (PC) is the one of the most common cancers among men in Australia and other parts of the world.  The E6–associated protein (E6AP) is an E3 ligase playing a key role Human Papilloma Virus (HPV) dependent carcinogenesis largely by targeting the p53 tumour suppressor. Recent work from our lab, and others, revealed a role for E6AP also in HPV-independent cancers, which includes B-lymphoma1. Importantly, we have recently shown that E6AP expression levels are elevated in PC2. Since p27 has been shown to be targeted by E6AP in vitro and in vivo3, we asked whether p27 is targeted by E6AP in PC? Protein p27 negatively regulates cell cycle by targeting Cdk2/cyclin E and Cdk2/cyclin A. In many cancers, including breast, ovarian, lung, and oral, the expression levels of p27 is low, or it becomes inactivated thereby supporting the proliferation of cancer cells and disease progression. Variation in p27 expression level correlates with poor prognosis and therapeutic efficiency in certain cancers4. Other studies have shown that p27 is deregulated in PC5.These initial data prompted us to hypothesis that E6AP down regulates p27 expression in PC. To elucidate the role of E6AP in regulating p27 in PC we have knocked down (KD) E6AP in PC xenografts and found an up-regulation of p27 expression. Initial data will be presented on the involvement of E6AP-p27 axis in the regulation of PC cell growth.

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