Abstract 327: Altered expression of insulin receptor isoforms in breast cancer

Abstract

Abstract Human insulin receptor (INSR) isoform A (IR-A), one of the two primary isoforms of INSR, constitutes an important therapeutic target for the development of anticancer drugs. There is also crucial need to develop a quick and sensitive method to accurately measure each of the two isoforms in humans. A specific quantitative real-time PCR-based assay has been developed to distinguish IR-A from insulin receptor isoform B (IR-B). This assay provides greater sensitivity, reproducibility, and clinical applicability than previously established methodologies. We used this assay to evaluate the mRNA expression levels of the IR-A and IR-B as well as multiple tumor proliferation markers in breast tumor tissues. Results revealed a significant decrease in IR-B mRNA expression leading to a relative increase in IR-A mRNA proportion in tumor samples compared to normal breast tissue samples. We also identified a novel positive correlation between increased IR-A: IR-B mRNA ratio and cancer proliferation markers, including Ki67. Furthermore, we observed a statistically significant difference of IR-A: IR-B mRNA ratio between luminal-A and -B breast cancer subtypes. These results suggest that IR-A is the predominant isoform of insulin receptor in breast cancer and highlights the potential value of characterizing changes in the IR-A: IR-B mRNA ratio as a therapeutic indicator for drugs that target insulin growth factor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 327. doi:10.1158/1538-7445.AM2011-327