Insulin signals through IGF-IR in insulin receptor knockout breast cancer cell line

Abstract

Breast cancer is a common malignancy observed more in females than in males. In breast cancer there is an upregulation of the IGF system. Upregulation of insulin and InsR are associated with poor patient prognosis. In order to understand the role of InsR in breast cancer biology, an InsR knockout cell line was created from MCF-7L breast cancer cells. Clone 35 showed loss of InsR expression, despite this loss, clone 35 showed activation of p-Akt and p-MAPK on stimulation with insulin. The hypothesis was developed that in the InsR knockout cell line insulin bound to IGF-IR and activated signaling. This hypothesis was proven by developing a knockout model, then using InsR and IGF-IR specific inhibitors on clone 35 to suggest the involvement of IGF-IR in activation through insulin. The following research substantiate the claims and provide a new understanding in the role of InsR and IGF-IR in breast cancer biology.