Cellular Response to Growth Factors and Doxorubicin of Breast Cancer Cells with Different Insulin Receptor Isoform

Insulin receptor (IR) plays a crucial role in cellular growth and proliferation through the regulation of metabolism. IR-A and IR-B isoforms are expressed by differential splicing of the IR gene, where IR-A modulates proliferation through inducing growth signaling factors, while IR-B signals primarily for metabolic pathways. Therefore, overexpression of IR-A in humans can lead to tumorigenic activity, which can be observed in endocrine-resistant breast cancers. IR also interacts with Insulin-like Growth Factors (IGF) along with IGF receptors in the tyrosine kinase receptor family.

In this study, breast cancer cell lines derived from MCF-7L with various IR isoform phenotypes were characterized through their response to various growth factors and resistance to doxorubicin, a common chemotherapy drug, measured by MTT assay. Here, we demonstrated a synergistic effect of the two IR isoforms in response to the ligands and in developing resistance to chemotherapy drugs. Furthermore, estradiol and growth ligands (Insulin and IGF-I) together provide a greater synergistic effect in MCF-7L cells compared to IR-A and IR-B cells. Further investigation will include co-infection of tagged IR-A and IR-B isoforms without endogenous IR expression to compare with the parent MCF-7L cell line, and their dose response to growth factors tested in this project.