Therapeutic Development of an Aptamer against the Dangerous side of SATB1

Proposal Placed in Dropbox. The link is http://dl.dropbox.com/u/11745574/Proposal---Aptamer%20Stream%20%28September%202010%29%207.docx

DNA-Binding SATB1 (Special AT-rich sequence-binding protein-1) shown in Figure 1 (1) is a protein encoded in humans by the SATB1 gene. Its functions have been found to include double stranded DNA-binding, sequence-specific DNA binding, transcription factor activity and transcription repressor activity (1). The protein plays a role in the regulation of gene expression in the differentiation and activation of T cells. This makes it very important for an individual’s immune system (2). It has now been known to also play a major role in the development of aggressive breast cancer because of its ability to control the expression of thousands of genes, by reorganizing the chromatin organization and transcription profiles of breast tumors.
Figure 1:http://en.wikipedia.org/wiki/File:Protein_SATB1_PDB_1yse.png

In vitro studies that have been conducted showed a reduction in SATB1 expression in highly metastatic cell lines reduced the invasiveness of those cells as well as their capability for unattached growth. Aggressive cancer cells need unattached growth in order for them to move through the blood and lymph vessels. (2) This in fact proves that the inhabiting of SATB1 will hinder it from increasing the growth of aggressive cancer tumors. There are no known successful aptamers that have been developed as therapeutics against SATB1.

An aptamer if successful would be very useful as a therapeutic against the SATB1 protein. Inhibiting the functional pathway of SATB1 would prevent its reprogramming of the genome to change the expression of genes that encourage the metastasizing of breast cancer cells. With that said, the aim is to develop an aptamer with a high enough affinity of specificity to bind to SATB1 in order to prevent it from being a “master regulator”. Like most anti-cancer drugs any therapeutic development against SATB1 expressed by breast cancer cells will also have an adverse effect on normal cells. Researching what types of cells are likely to express SATB1 could be useful in terms of a preventative measure. In vitro selection would be the method used to select against SATB1. Figure 2 is an outline of what is discussed in this abstract.FIGURE 2) When Breast cancer cells express SATB1 protein, SATB1 reorganizes hundreds of genes thereby leading to the metastasizing of breast cancer cells. The inhibiting of SATB1 could prevent this from happening.