Targeting CaSR/GABAB R1 Heterodimers to Treat Bone Metastases in Breast Cancer
Abstract
The goal of this project are to test whether genetic or pharmacologic inhibition of CaSR/GABAB R1 heterodimers can antagonize the growth and/or survival of breast cancer cells exposed to high extracellular calcium in vitro or grown in animal models of bone metastases in vivo. Over this past 3rd year of the project, we continued to make progress on generating tetracycline-regulated knockdown of the CaSR and GABAB R1 in breast cancer cells. We also performed initial experiments examining how genetic knockdown of PTHrP and the CaSR affected the formation and growth of osteolytic bone metastases in MDA-MB-231 breast cancer cells in nude mice. As expected knocking down PTHrP expression reduced the size of osteolytic metastases but, surprisingly, knocking down CaSR expression actually increased the size of osteolytic lesions. We are continuing to validate and better understand these results while waiting for the new regulated knockdown cell lines for the CaSR and GABAB R1. We received a no-cost extension to finish up these experiments but they were further delayed by the COVID situation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1109484
Entities
People
- John Wysolmerski
Organizations
- Yale University