Insulin-like growth factor-1 regulates vascular endothelial growth factor synthesis and secretion in mammary epithelial cells

The mammary circulatory system supports mammary growth and lactation by supplying oxygen and nutrients. Insulin-like growth factor 1 (IGF1) is essential for mammary gland development, yet its involvement in angiogenic regulation remains unclear. This study investigated whether IGF1 stimulates vascular endothelial growth factor (VEGF) production in mammary epithelial cells and explored the underlying signaling pathways. IGF1 increased VEGF mRNA expression in a bovine mammary epithelial cell line and in HC11 cells, and enhanced VEGF promoter activity and secretion in HC11 cells in a dose-dependent manner. Conditioned medium from IGF1-stimulated HC11 cells promoted tube formation in HUVECs, which was attenuated by a VEGFR inhibitor. IGF1 rapidly induced ERK1/2 and Akt phosphorylation, and inhibitors of these pathways suppressed VEGF secretion. These findings suggest that IGF1 upregulates VEGF via the MEK-ERK1/2 and PI3K-Akt pathways, thereby promoting mammary angiogenesis and contributing to mammary gland development and lactation efficiency.