Accession Number : ADA555934


Title :   Hormonal Resistance And Metastasis ER-Coregulartor-Src Signaling Targeted Therapy


Descriptive Note : Annual rept. 1 Sep 2010-31 Aug 2011


Corporate Author : TEXAS UNIV AT SAN ANTONIO HEALTH SCIENCE CENTER


Personal Author(s) : Vadlamudi, Ratna


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a555934.pdf


Report Date : Sep 2011


Pagination or Media Count : 56


Abstract : The estrogen receptor (ER) is implicated in the progression of breast cancer. Despite positive effects of hormonal therapy, initial or acquired resistance to endocrine therapies frequently occurs. To establish the significance of ER-Src axis in PELP1 and HER2 mediated therapy resistance, we have generated model cells that stably express Src-shRNA under conditions of PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2 mediated activation of Src and MAPK activation in resistant model cells. Pharmacological inhibition of Src using dasatinib, an orally available inhibitor substantially inhibited the growth of therapy resistant MCF7-PELP1, MCF7-HER2, and MCF7-Tam model cells in proliferation assays. In post-menopausal xenograft based studies, treatment with dasatinib significantly inhibited the growth of therapy resistant cells. Since PELP1, HER2, and Src kinase are commonly deregulated in breast cancers, combination therapies using both endocrine agents and dasatinib may have better therapeutic effect by delaying the development of hormonal resistance.


Descriptors :   *HORMONES , *METASTASIS , BREAST CANCER , CELLS , ESTROGENS , SENSE ORGANS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE