Accession Number : ADA613320


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


Descriptive Note : Final rept. 1 Sep 2011-31 Aug 2014


Corporate Author : CINCINNATI UNIV OH


Personal Author(s) : Zhang, Xiaoting


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a613320.pdf


Report Date : Sep 2014


Pagination or Media Count : 37


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-alpha, 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 further tested and optimized the RNA aptamers obtained by SELEX method, based on its structure and ability to inhibit breast cancer cell growth, migration and estrogen-dependent gene expression. Through these studies, we have obtained one most promising RNA aptamer that can specifically disrupt the ER/MED1 interaction. Importantly, this aptamer not only greatly inhibited breast cancer growth, migration and ER target gene expression in vitro, but also blocked tumor growth in an orthotopic xenograft mouse model.


Descriptors :   *BREAST CANCER , GENE EXPRESSION , RIBONUCLEIC ACIDS , TISSUES(BIOLOGY)


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE