Accession Number : ADA457498


Title :   The Role of Semaphorin 3B (SEMA3B) in the Pathogenesis of Breast Cancer


Descriptive Note : Annual summary 1 Apr 2003-31 Mar 2006


Corporate Author : TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER


Personal Author(s) : Castro-Rivera, Emely


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a457498.pdf


Report Date : Apr 2006


Pagination or Media Count : 15


Abstract : Semaphorin 33 is a secreted member of the semaphorin family important in axonal guidance which we and others have recently shown can act as a tumor suppressor by inducing apoptosis either by re-expression in tumor cells or applied as a soluble ligand. The common method of inactivation of SEMA3B is by allele loss and HDAC. We study the mechanism of SEMA3B effect on breast cancer cells. We found that vitamin D3 and TGF beta 1 can induce SEMA3B protein and promoter activation. We found that VEGF165 which is reported to bind to neuropilin (NP) significantly decreased the anti-mitotic effect of transfected or secreted SEMA3B on breast cancer cells. By contrast VEGFi2i a VEGF variant that lacks binding to NPs receptors had no effect on SEMA3B growth suppressing activities. In addition SEMA3B competed for binding of 1251-VEGF165 to lung and breast cancer cells. We also found that SEMA3B apoptotic and anti-proliferative effect on cancer lines it is in part by the inhibition of Akt pathway. In conclusion we hypothesize that VEGF165 produced by tumor cells acts as an autocrine survival factor and SEMA3B mediates its tumor suppressing effects at least in part by blocking this VEGF autocrine activity and by inhibiting the Akt pathway.


Descriptors :   *BREAST CANCER , *APOPTOSIS , ACTIVATION , NEOPLASMS , LIGANDS , LUNG , GUIDANCE , SOLUBILITY , INHIBITION , SURVIVAL(PERSONNEL) , CELLS(BIOLOGY) , PATHOGENESIS , RECEPTOR SITES(PHYSIOLOGY) , SUPPRESSORS , NERVE FIBERS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE