Cory Abate-Shen

....

..Here, we review recent findings concerning the roles of Nkx3.1 in development and discuss how its normal function is disrupted in processes of early prostate carcinogenesis...

..Here we discuss opportunities and challenges for the application of GEM models in prevention research, as well as strategies to maximize their relevance for human cancer...

....

..Together, our findings suggest a generalized therapeutic approach to target c-Myc activation in prostate cancer by combinatorial targeting of the PI3K → Akt → mTOR and ERK1/2 MAPK signaling pathways...

..These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer...

..Our results reveal the inherent plasticity of basal cells, and support a model in which different cells of origin generate distinct molecular subtypes of prostate cancer...

..Our findings suggest that dual targeting of the Akt and mTOR signaling pathways using MK-2206 and ridaforolimus (MK-8669) may be effective for treatment of CRPC, particularly for patients with deregulated Rb pathway activity...

..We therefore propose that combination therapy targeting AKT/mTOR and ERK MAPK signaling pathways may be an effective treatment for patients with advanced prostate cancer, in particular those with hormone-refractory disease...

..In conclusion, simultaneous heterozygosity of Pten and Trp53 accelerates prostatic tumorigenesis in this mouse model of prostate cancer independently of loss of heterozygosity of either gene...

..Our integrated analyses of mouse and human bladder cancer provide a rationale for investigating mTOR inhibition for treatment of patients with invasive disease...

..Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead...

..Protocols are also provided on the use of these models for the preclinical evaluation of new chemical entities, with mTOR inhibitors shown as an example...

..To investigate the relationship between diabetes and metformin use with outcomes after radical prostatectomy (RP) for clinically localized cancer...

....

..We propose that regulation of chromatin status by Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions of target genes represents an important means of regulating the gene expression during development...

..Here we discuss the implications of our recent work showing that transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery during development...

..Our findings illustrate a hitherto unappreciated spatial coordination of transcription factors with the Polycomb complex for appropriate regulation of gene expression programs during development...

..Our results suggest that DLX transcription factors serve to integrate and transduce feather patterning signals to downstream effector molecules...

..Taken together, our focused analyses of Msx homeoproteins will provide general paradigms for addressing the functional specificities of other homeoproteins in vivo. ..

..1 protein expression. These mice will provide a valuable model for exploring the reversibility of prostate carcinogenesis in vivo. ..

..Therefore, it is of the utmost clinical significance to understand the evolution of androgen-independent prostate cancer and to delineate the underlying molecular pathways. ..

..Taken together, our focused analyses of Msx homeoproteins will provide general paradigms for addressing the functional specificities of other homeoproteins in vivo. ..

..More useful for the present proposal is her observation that injection at stage 17 blocks differentiation of feather follicles. Abate proposes to develop this overexpression phenotype as a quantitative assay for function. ..

..Taken together, our focused analyses of Msx homeoproteins will provide general paradigms for addressing the functional specificities of other homeoproteins in vivo. ..

..1 in development will be analyzed by investigating its role in the male urogenital system, by examining its cell autonomy, and its over-expression in reconstituted prostatic tissue. ..

..1 in the regulation of gene expression in the developing murine CNS and will also provide general insight into the molecular mechanisms that control gene transcription during mammalian neurogenesis...

..Therefore, it is of the utmost clinical significance to understand the evolution of androgen-independent prostate cancer and to delineate the underlying molecular pathways. ..