Old Receptors, New Treatment Strategies for Breast Cancer.

摘要

We have made considerable progress towards each project proposed in the original grant. For Aim 1, we have developed TRFRET assays that can be adapted for high throughput screening to identify chemical activator of CARM1 for breast cancer differentiation therapy. For Aim 2, we have developed isogenic MDA-mb-468 cell line inducibly express either ER or ER . These cell lines have been validated to form xenograft tumors in nude mice. We have begun to assess whether 18 Fluoro-17-estradiol could detect ER-positive breast tumors in vivo and thus suitable for in vivo PET imaging. We have optimized conditions to use a commercial ER antibody for immunohistochemistry. Using Tissue Microarray (TMA), we demonstrated that 25% of triple negative breast tumors express significant amount of ER. Using MDA-mb-468-ER cell line, we performed RNA-sequencing and identified ER target genes. These target genes will be tested in tumor samples from clinical trial to determine whether estrogen treatment activated ER in patients. For Aim 3, we have determined pharmacokinetics of one of the ER/heterodimer-selective phytoestrogens, cosmosiin, in ACI rat model and showed that serum concentration of cosmosiin could reach M that is sufficient to induce ER/heterodimer in vivo.