Estrogen-Related Receptor Alpha As A Novel Biomarker For Breast Cancer

OBJECTIVES:

• Identify by mass spectroscopy and site-specific mutagenesis the post-translational modifications of estrogen-related receptor alpha (ERRα1) that are responsible for ERRα1 function as a constitutive activator rather than a down-modulator of transcription of estrogen response element-regulated genes in tumors of patients with breast cancer.
• Produce a panel of monoclonal antibodies to ERRα1 by standard hybridoma methods that can be used to distinguish between the activator and repressor forms of this receptor in these patients.
• Validate the utility for immunohistochemistry (IHC) assays of some of the ERRα-specific sera by performing IHC and quantitative real-time PCR on some primary breast carcinomas.
• Correlate the results of IHC studies on archival paraffin sections of primary breast tumors using monoclonal antibodies to ERRα1, ERRα1 status, currently assayed biomarkers, and course of treatment with patient outcomes.

OUTLINE: Breast tumor tissue samples are obtained from a tissue bank in the form of frozen tumors and paraffin-embedded sections on microarray blocks. Monoclonal antibodies (MOABs) to ERRα1 are produced using antigens in these tissue samples and immunohistochemical studies are performed using the MOABs. Cytogenetic studies are performed on DNA purified from these tissue samples.