Accession Number : ADA592120


Title :   Targeting MED1 LxxLL Motifs for Tissue-Selective Treatment of Human Breast Cancer


Descriptive Note : Annual rept. 1 Sep 2012-31 Aug 2013


Corporate Author : CINCINNATI UNIV OH


Personal Author(s) : Zhang, Xiaoting


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a592120.pdf


Report Date : Sep 2013


Pagination or Media Count : 36


Abstract : Breast cancer is the most common type of cancer and a leading cause of death among Western women. Most breast cancers (75%) express ER , and antiestrogens have been widely used in their treatment. However, acquired resistance and unwanted side effects in other estrogen-responsive tissue such as uterus have greatly limited their use. The objective of this study to isolate RNA aptamers that specifically target the estrogen receptor interacting NR boxes/LxxLL motifs of the MED1 protein and test their efficacy on breast cancer cell growth both in vitro and in vivo by utilizing a pRNA nanodelivery system for tissue-selective therapy. In this funding period, we have generated large amount of highly purified MED1 protein and RNA aptamer library. We further carried out and optimized SELEX experiments to select RNA aptamers that specifically bind wild type but not mutant MED1 LxxLL motifs. After 6 rounds of selections, we have obtained and tested 11 RNA aptamers. With our establishment of RNA nanoparticle system, we are now ready to further test these RNA aptamers on ER-mediated functions and breast tumor growth both in vitro and in vivo.


Descriptors :   *BREAST CANCER , CELLS(BIOLOGY) , DEATH , ESTROGENS , RIBONUCLEIC ACIDS , TISSUES(BIOLOGY)


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE