Phosphatase and tensin homolog (PTEN) is the second most frequently deleted human tumor suppressor gene. PTEN mutation also was found to be the cause of three autosomal dominant tumor predisposition syndromes. Dr. Hong Wu researches the molecular mechanism of PTEN controlled tumorigenesis, using a combination of molecular genetics, cell biology and biochemical approaches. By analyzing cells and animals lacking the PTEN tumor suppressor, Wu and her colleagues have demonstrated that PTEN negatively regulates stem cell self-renewal, proliferation and survival. Thus, their study provides a strong link between stem cell biology and cancer biology and suggests that tumors may originate through the transformation of stem cells. They also established various animal models for human cancers, including mammary and prostate cancer models. These murine cancer models offer unique tools for both exploring the molecular mechanism underlying human cancers and for the development of new therapies.
Wu's recent study demonstrated that PTEN controls p53 protein level and transcription activity, which provides a novel mechanism by which the loss of PTEN can functionally control two "hits" in the course of tumor development by concurrently modulating p53 activity.
Selected Cancer-Related Publications:
Groszer M, Erickson R, Scripture-Adams DD, Dougherty JD, Le Belle J, Zack JA, Geschwind DH, Liu X, Kornblum HI, Wu H. PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry. Proc Natl Acad Sci U S A. 2006; 103(1): 111-6.
Wang S, Garcia AJ, Wu M, Lawson DA, Witte ON, Wu H. Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci U S A. 2006; 103(5): 1480-5.
Lei Q, Jiao J, Xin L, Chang CJ, Wang S, Gao J, Gleave ME, Witte ON, Liu X, Wu H. NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss. Cancer Cell. 2006; 9(5): 367-78.
Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, Whale AD, Martinez-Diaz H, Rozengurt N, Cardiff RD, Liu X, Wu H. PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Cancer Cell. 2003; 3(2): 117-30.
Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, Thomas GV, Li G, Roy-Burman P, Nelson PS, Liu X, Wu H. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell. 2003; 4(3): 209-21.