The COOH-terminus of the IGF-1Ec Isoform Enhances the Proliferation and Migration of Human MCF-7 Breast Cancer Cells.

Background/Aim: The insulin-like growth factor-1 (IGF-1) signaling is well implicated in cancer biology, however the potential roles of the distinct IGF-1 isoforms in human malignancies are largely unknown. Recently, the carboxyl-terminal of the IGF-1Ec variant (hEc; 24aa) has been associated with osteosarcoma and prostate cancer. Herein, we investigated the potential role of hEc in breast cancer. Materials and Methods: Synthetic hEc peptide was administrated to MCF-7 and MDA-MB-231 breast cancer cells. In addition MCF-7 cells were engineered to overexpress hEc. The proliferation and migratory capacities in response to hEc were analyzed using MTT, trypan blue and wound healing/scratch assays, while the activation of the ERK/AKT signaling pathways were investigated using phospho western blotting. Results: We found that exogenous administration of hEc stimulated the proliferation of estrogen-responsive MCF-7, but not that of hormone-resistant MDA-MB-231 cells. In addition, MCF-7 cells stably-overexpressing hEc acquired an increased proliferation rate and migratory capacity, as well as, enhanced ERK1/2 phosphorylation, compared to mock and wild-type cells. Conclusion: hEc stimulates the proliferation and migration of MCF-7 breast cancer cells and enhances the intracellular ERK1/2 signaling.