研究领域
Prostate cancer, Retinoblastoma (RB) E2F transcription factors, Androgen Receptor
Prostate carcinoma is the most commonly diagnosed cancer in men, and the second leading cause of death due to cancer in Western civilization. Androgen ablation therapy is effective in treating androgen-dependent tumors, but eventually, androgen-independent tumors recur and are refractory to conventional chemotherapies. Tumor recurrence is often due to reactivation of androgen receptor (AR) signaling but is also accompanied by deregulation of cell cycle and proliferative controls. The mechanism by which AR promotes proliferation has not been established. The RB/E2F pathways has been shown to be deregulated in prostate tumors, but recent studies indicate that E2F3 overexpression is predictive of a poor clinical outcome. However it is currently unknown how E2F3 contributes to tumorigenesis. My lab is dedicated to defining the molecular mechanisms that govern tumor progression. We currently have three main projects in the lab:
Regulation of AR dependent gene expression and cellular proliferation in prostate cancer
The interplay between E2F3 overexpression, RB deregulation and the AR in prostate tumorigenesis
The role of E2F3B isoform in prostate tumorigenesis
近期论文
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Honglin Chen, Stephen J. Libertini, Clifford G. Tepper, Hsing-Jien Kung, Michael George, Satya Dandekar, Bushra el-Bataina, Paramita M. Ghosh, Maria Mudryj. (2010) Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. Endocrine-related Cancer Endocr Relat Cancer. 2010 Jul 15.
Honglin Chen, Stephen J. Libertini, Yu Wang, Hsing-Jien Kung, Paramita Ghosh, Maria Mudryj. (2010) Erk Regulates Calpain 2 Induced Androgen Receptor proteolysis in CWR22 Relapsed Prostate Tumor Cell Lines. Journal of Biological Chemistry 285(4):2368-74.
Beolla, RG, Yu Wang, Alfredo Asuncion, Karim Chamie, Salma Siddiqui, Maria Mudryj, Javed Siddiqui, Arul M. Chinnaiyan, Rohit Mehra, Ralph W. deVere White and Paramita. M. Ghosh ( 2009) Cellular Localization of Filamin A in Advanced Hormone Refractory Prostate Cancer: Immunohistochemical Correlation with Metastases. Clinical Cancer Research 15(3):788-96.
Hong-Lin Devlin and Maria Mudryj. (2009) Progression of Prostate Cancer: Multiple Pathways to Androgen Independence. Cancer Letters 274 (2):177-86.
Honglin Devlin, Phillip C. Mack, Rebekah A. Burich, Paul H. Gumerlock, Hsing-Jien Kung, Maria Mudryj and Ralph W. deVere White. (2008) Impairment of the DNA Repair and Growth Arrest Pathways by p53R2 Silencing Enhances DNA Damage-Induced Apoptosis in a p53 Dependent Manner in Prostate Cancer (CaP) Cells. Molecular Cancer Research 6(5), 808-818.
Maria Mudryj, Elizabeth Reay, Satya Dandekar, Laurel Beckett, Ralph DeVere White and Regina Gandour-Edwards. (2007) A novel p53/p130 axis in bladder tumors. Urology 70, 608-12.
Stephen J. Libertini, Clifford G. Tepper, David M. Asmuth, Hsing-Jien Kung, Maria Mudryj. (2007) Evidence for Calpain mediated Androgen Receptor Cleavage as a Mechanism for Androgen Independence and Potential Therapeutic Target in Prostate Tumors. Cancer Research 69, 9001-5.
Stephen Libertini, Clifford G. Tepper, Moraima Guadalupe, Ying Lu, David M. Asmuth and Maria Mudryj. (2006) E2F1 expression in LNCaP prostate cancer cells deregulates androgen dependent growth, suppresses differentiation, and enhances apoptosis. Prostate 66, 70-81.
Stephen J. Libertini, Brian Robinson, Navdeep K. Dhillon, Danielle Glick, Michael George, Satya Dandekar, Jeffrey P. Gregg, Earl Sawai, and Maria Mudryj. (2005) Cyclin E both regulates and is regulated by calpain 2, a protease associated with metastatic breast cancer phenotype. Cancer Research, 65, 10700-10708.