Accession Number : ADA535546


Title :   Hormonal Resistance and Metastasis: ER-coregulator-Src Signaling Targeted Therapy


Descriptive Note : Annual rept. 1 Sep 2009-31 Aug 2010


Corporate Author : TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO


Personal Author(s) : Vadlamudi, Ratna K


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a535546.pdf


Report Date : Sep 2010


Pagination or Media Count : 57


Abstract : The estrogen receptor (ER), is implicated in the progression of breast cancer. Endocrine therapy is shown to have a positive effect on the treatment of breast cancer; however, initial or acquired resistance to endocrine therapies frequently occurs. In this study, we have generated model cells that have defects in either ER coregulator PELP1 or Src signaling axis. Using these models, we demonstrated that PELP1-Src axis play a key role in ER- extranuclear actions. Our data suggest that PELP1 and Src kinase axis also play an essential role in enhancing cell migration and metastasis. Pharmacological inhibition of Src kinase using dasatinib or Src knock down by shRNA significantly inhibited E2-mediated extranuclear actions in therapy resistant cells. The results from our study showed that ER-Src axis play an important role in promoting hormonal resistance by protooncogenes such as HER2, PELP1 and blocking this axis prevents the development of hormonal independence. Since PELP1 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 :   *BREAST CANCER , THERAPY , PHOSPHORUS TRANSFERASES , METASTASIS , HORMONES , ESTROGENS


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE