Estrogen Receptor/MAPK Crosstalk as a Mechanism of Radiation Resistance of Breast Cancer
Abstract
Loss of estrogen receptor (ER) function has been associated with hyperactive ERK1/2, which culminates in aggressive, radiation resistant cancers. The ERK1/2 pathway has also been linked to DNA damage and repair, with multiple proteins involved in DNA repair being transcriptionally regulated through ERK1/2-dependent signaling. An increased DNA repair capacity in ER-a negative breast tumors has been implicated as a mechanism of radioresistance. We postulate that the mechanism of development of radiation resistance in the ER-a negative breast cancer cells involves a dynamic interplay between the ERK1/2 pathway and DNA repair proteins. We compared ER-a positive and negative cells for expression levels of ERK1/2 and DNA repair proteins involved in the repair of radiation-induced double strand breaks. Preliminary data obtained from clonogenic cell survival assays showed that ER-a positive cells were more radiosensitive compared with the ER-a negative cells. These cell lines are also being compared for the expression of ERK1/2 and its downstream proteins and proteins involved in DNA repair by Western blot analysis. We are also evaluating the ability of inhibitors of the ERK1/2 pathway to restore radiosensitivity to the ER-a negative cell lines. The effect of these inhibitors on expression of DNA repair proteins and their ability to restore ER-a expression will also be tested. The outcome of these studies will have a potential impact in the clinic and benefit breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA548989
Entities
People
- Anupama Munshi
Organizations
- The University of Texas MD Anderson Cancer Center