Nuclear Receptor Interactions in Breast Cancer: The Role of Kinase Signaling Pathways
Abstract
Retinoids are vitamin A derivatives, which cause growth inhibition, differentiation and/or apoptosis in various cell types, including some breast cancer cells. In general, estrogen receptor (ER)-positive cells are retinoic acid (RA) sensitive, whereas ER-negative cells are resistant. I have showed that ER-negative MDA-MB-231 cells and MDA-MB-468 cells are strongly growth inhibited by retinoids in combination with PKC inhibition, and inhibition of PKC in particular. In this report, I show that the PKC inhibitor GF1092O3X increases gene regulation by RA, as shown by microarray studies, and identify certain genes/pathways that may be important. I also show that apoptosis following treatment with RA plus the PKC delta specific inhibitor Rottlerin involves loss of mitochondrial transmembrane potential and release of cytochrome c into the cytosol. Further, I report that while GF1O92O3X decreases phosphorylation of RARa in MDA-MB-231 cells, stable expression of ER alpha or beta in these cells leads to an increase in RA alpha or beta osphorylation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA444023
Entities
People
- Filippa Pettersson
Organizations
- McGill University