Oesophageal Cancer Research – Assoc Prof Denver Hendricks (Insulin receptor isoforms)
- Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town
- Email: Denver.firstname.lastname@example.org
Title of the project
Insulin receptor isoforms as therapeutic targets in oesophageal cancer
Highlights of the project
Compelling evidence in the literature and results obtained in our laboratory indicate that EGFR (epidermal growth factor receptor) and IGF1R (insulin-like growth factor receptor type 1) play critical roles in providing proliferative and survival signals to oesophageal cancer cells. These receptors provide attractive targets in the chemotherapeutic treatment of oesophageal cancer, and numerous inhibitors to EGFR and IGF1R are currently available to test this hypothesis in oesophageal cancer. However, in many cancers, IR-A (insulin receptor isoform A, a splice variant of the classic insulin receptor, isoform B) is over-expressed and heterodimerizes with IGF1R. Results in the literature suggest that IR-A/IGF1R receptor hybrids also provide survival and proliferative signals. The aim of this study is to determine the expression status of IR-A in oesophageal cancer cells, to determine the presence of IR/IGF1R receptor hybrids, and determine the effect of these hybrid receptors in oesophageal cancer cells treated with EGFR and IGF1R inhibitors.
Our results show that oesophageal cancer cells express a variant of the insulin receptor that is activated by insulin and another growth factor, IGFII. In response to treatment with either insulin or IGFII, cancer cells expressing this variant of the insulin receptor grow faster than cells that lack this variant of the insulin receptor. This suggests that circulating insulin levels and levels of IGFII could affect the growth of oesophageal tumours. This has important health implications for people who have elevated plasma insulin levels, regarding their risk to tumorigenesis.