Targeting MED1 LxxLL Motifs for Tissue-Selective Treatment of Human Breast Cancer
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 5 rounds of selections, we have now obtained several RNA aptamers for further studies. With our in vivo orthotopic xenograft experiments confirming MED1 requirements for breast tumor growth, we are now ready to further test these RNA aptamers both in vitro and in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2012
- Accession Number
- ADA567824
Entities
People
- Xiaoting Zhang
Organizations
- University of Cincinnati