Accession Number:

ADA550799

Title:

Estrogen Receptor/MAPK Crosstalk as a Mechanism of Radiation Resistance of Breast Cancer

Descriptive Note:

Final addendum 20 Aug 2010-19 Feb 2011

Corporate Author:

M D ANDERSON CANCER CENTER HOUSTON TX

Personal Author(s):

Report Date:

2011-03-01

Pagination or Media Count:

19.0

Abstract:

Loss of estrogen receptor ER function has been associated with hyperactive ERK12, which culminates in aggressive, radiation resistant cancers. The ERK12 pathway has also been linked to DNA damage and repair, with multiple proteins involved in DNA repair being transcriptionally regulated through ERK12-dependent signaling. An increased DNA repair capacity in ER- negative breast tumors has bee implicated as a mechanism of radioresistance. We postulate that the mechanism of development of radiation resistance in the ER- negative breast cancer cells involves a dynamic interplay between the ERK12 pathway and DNA repair proteins. We compared ER- positive and negative cells for expression levels of ERK12 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- positive cells were more radiosensitive compared with the negative cells. These cell lines are also being compared for the expression of ERK12 and its downstream proteins and proteins involved in repair by Western blot analysis. We are also evaluating the ability of inhibitors of the ERK12 pathway to restore radiosensitivity to the ER negative cell lines. The effect of these inhibitors on expression of DNA repair proteins and their ability to restore ER- expression will also tested. The outcome of these studies will have a potential impact in the clinic and benefit breast cancer patients

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE