Prostate cancer (PrCa) is the second leading cause of cancer related death in North American men. In the majority of cases, PrCa becomes androgen-independent (Al)or hormone refractory. Progression to Al PrCa is multi-factorial and can be attributed to activation of pro-survival cell signalling by circulating growth factors, aberrant androgen receptor (AR) transcription and evasion of apoptosis. We have shown shown that the oncoprotein, Beta-catenin, can alter AR transcription and potentially contribute towards aberrant growth during Al PrCa. We have also shown that the tumour suppressor, PTEN, can negatively regulate Beta-catenin/Tcf signalling. Using both loss and gain of function systems we proposed to further evaluate the role of Beta-catenin in PrCa. Specifically, a prostate specific PTEN knock-out mouse will allow us to evaluate expression and distribution of Beta-catenin and molecules known to regulate its activity. We will also employ the use of LNCaP PrCa cells stably transfected with PTEN under an inducible Tet regulated promoter. These cells will be assessed for growth and PSA secretion in tumours carried as xenografts. These novel in vivo tools will allow understanding to the role of Beta-catenin has in Al PrCa.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F09 (20))
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Jakowlew, Sonia B
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Ruscetti, M; Dadashian, E L; Guo, W et al. (2016) HDAC inhibition impedes epithelial-mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer. Oncogene 35:3781-95
Ruscetti, Marcus; Quach, Bill; Dadashian, Eman L et al. (2015) Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis. Cancer Res 75:2749-59
Hübner, Anette; Mulholland, David J; Standen, Claire L et al. (2012) JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate. Proc Natl Acad Sci U S A 109:12046-51
Mulholland, David J; Kobayashi, Naoko; Ruscetti, Marcus et al. (2012) Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res 72:1878-89
Mulholland, David J; Tran, Linh M; Li, Yunfeng et al. (2011) Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell 19:792-804
Mulholland, David J; Xin, Li; Morim, Ashkan et al. (2009) Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model. Cancer Res 69:8555-62
Mosessian, Sherly; Avliyakulov, Nuraly K; Mulholland, David J et al. (2009) Analysis of PTEN complex assembly and identification of heterogeneous nuclear ribonucleoprotein C as a component of the PTEN-associated complex. J Biol Chem 284:30159-66
Chang, Chun-Ju; Mulholland, David J; Valamehr, Bahram et al. (2008) PTEN nuclear localization is regulated by oxidative stress and mediates p53-dependent tumor suppression. Mol Cell Biol 28:3281-9