Accession Number : ADA508242


Title :   Mechanisms of Abnormal Growth Regulation in Prostatic Adenocarcinoma Using Abi1/Hssh3bp1 Conditional Knockout Mouse Model


Descriptive Note : Annual rept. 19 May 2008-18 May 2009


Corporate Author : NEW YORK BLOOD CENTER NY


Personal Author(s) : Kotula, Leszek ; Xiong, Xiaoling


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA508242


Report Date : JUN 2009


Pagination or Media Count : 70


Abstract : Prostate cancer is the most common type of cancer found in American men. The American Cancer Society estimates that there will be about 190,000 new cases and 27,000 deaths of prostate cancer in the United States in 2009. Genetic alterations of tumor suppressor genes are one of the most common causes of prostate cancer tumorigenesis. Our group identified Abi1/Hssh3bp1 as candidate prostate tumor suppressor gene. To understand the role of Abi1/Hssh3bp1 in prostate tumorigenesis we developed the conditional Abi1/Hssh3bp1 KO mouse. In the first funding period we expanded our mouse colony and set up specific breeding schemes for proposed prostate tumorigenesis mouse models i.e. for prostate-specific disruption of Abi1/Hssh3bp1 or simultaneous disruption of Abi1/Hssh3bp1 and PTEN genes. Cre recombinase-mediated disruption of the gene was confirmed in dissected prostates of animals with Abi1/Hssh3bp1 (fl/fl)PbCre(Tg/-) genotype. In addition we isolated Abi1/Hssh3bp1 (fl/fl) MEF cells and cloned cells lacking Abi1/Hssh3bp1 to be used for in vitro characterization of Abi1/Hssh3bp1-dependent cell growth regulation pathways. Toward that goal we also screened genomewide SH2 domain library with phosphotyrosine peptides derived from Abi1/Hssh3bp1 and identified several candidate Abi1/Hssh3bp1-binding SH2 domain-containing proteins. These protein-Abi1/Hssh3bp1 interactions will be further characterized using cells and animal tissue lacking Abi1/Hssh3bp1.


Descriptors :   *MICE , *GROWTH(PHYSIOLOGY) , *ANATOMICAL MODELS , *ABNORMALITIES , *PROSTATE CANCER , GENES , CLONES , SYNCHRONISM , COLONIES(BIOLOGY) , PROSTATE GLAND , IN VITRO ANALYSIS , NEOPLASMS , PEPTIDES , CELLS , TISSUES(BIOLOGY) , PRODUCTION


Subject Categories : MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE