Accession Number : ADB259879


Title :   Elucidating the Role of cAb1 and the Abi-Family of cAB1 Target Proteins in Cancer Development and Progression


Descriptive Note : Annual rept. 1 Jul 1999-30 Jun 2000


Corporate Author : DUKE UNIV MEDICAL CENTER DURHAM NC


Personal Author(s) : Courtney, Kevin ; Pendergast, Ann


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b259879.pdf


Report Date : Jul 2000


Pagination or Media Count : 51


Abstract : Abi-interactor (Abi) proteins bind and are phosphorylated by the non-receptor tyrosine kinases Abi and Arg. Two Abi family genes, Abi-1 and Abi-2, have been identified. Abi proteins demonstrate properties consistent with a potential tumor suppressor function. We investigated the role of Abi-l and Abi-2 proteins and their interactions with c-Abl and c- Abl-derived oncogenes in normal development and tumorigenesis. Abi-l and Abi-2 exhibit both unique and overlapping temporal-spatial patterns of expression during embryonic and post-natal mouse development. Abi-2 is enriched in regions of the central and peripheral nervous systems (CNS and PNS) pre- and post-natally. Abi-l is also enriched in regions of the post-natal brain, but is not enriched in the pre-natal CNS and is absent from examined PNS structures. Abi proteins undergo changes in phosphorylation during development. Examination of Abi proteins in the presence of oncogenic forms of Abl and Src revealed loss of Abi expression due to ubiquitin-mediated degradation. Abi proteins were down- regulated or exhibited aberrant patterns of expression in some glioblastoma multiforme samples compared to normal brain tissue. Degradation has yet to be observed in other tumor settings, including breast cancer-derived cell lines overexpressing members of the erbE family of receptor tyrosine kinases. These findings support both unique and shared roles for Abi-l and Abi-2 in mammalian development and suggest Abi degradation may be important in malignant transformation mediated by certain oncogenes.


Descriptors :   *SENSE ORGANS , *RECEPTOR SITES(PHYSIOLOGY) , *PHOSPHORUS TRANSFERASES , *ONCOGENIC VIRUSES , *BREAST CANCER , TISSUES(BIOLOGY) , DEGRADATION , BRAIN , PROTEINS , NEOPLASMS , PATTERNS , NERVOUS SYSTEM , GENES , EMBRYOS , CELLS(BIOLOGY) , ABNORMALITIES , FAMILIES(HUMAN) , TRANSFORMATIONS , SUPPRESSORS , TYROSINE , PHOSPHORYLATION


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE