Role of estrogen-related receptor alpha (ESRRA) in oral squamous cell carcinoma.

Abstract

e16009 Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies world over with one of the lowest rates of survival which has remained unchanged over the past many decades. Given this scenario, it is imperative to identify new therapeutic targets and molecular biomarkers to aid in better estimation of prognosis and treatment. Methods: Oligonucleotide based comparative genomic hybridization (aCGH) analysis in our laboratory has revealed that 3/8 OSCC samples show amplification of the gene ESRRA (estrogen related receptor alpha) located at chromosome 11q13.1. ESRRA is a member of the orphan nuclear receptor super family and is closely related to estrogen receptor (ER) alpha. ESRRA is known to modulate gene expression of a number of genes such as EGFR, VEGF etc. The transcriptional activity of ESRRA is regulated through the EGFR pathway. Recently many reports suggest the potential involvement of ESRRA in several tumors such as breast, prostate and ovarian cancer. Given this scenario, we wanted to study the role of ESRRA in OSCC. Real-time RT-PCR and western blot analyses showed that ESRRA is significantly up-regulated both at the transcript and protein levels in OSCC samples and precancerous lesions. Results: The expression profile of ESRRA is correlated well with aggressiveness of the cancer, suggesting that ESRRA may play an important role in the proliferation and metastasis of cancer. Conclusions: Treatment of cancer cell lines with the specific inhibitor XCT790 of ESRRA showed a significant decrease in cell viability. Treating the cells with XCT790 has provided an important insight into the unique interaction between ESRRA and EGFR which is a specific target of ESRRA. These preliminary results suggest that ESRRA might have a potential involvement in the progression of OSCC. This work is financially supported by CSIR and DBT, New Delhi.