PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C upregulation in breast cancer

• Published in: Journal of cancer research and clinical oncology 2011-11, Vol.137 (11), p.1587-1594
• Main Authors: Zhu, Chenfang, Qi, Xiaoliang, Chen, Yaning, Sun, Bo, Dai, Yalei, Gu, Yan
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Chromones - pharmacology; Female; Gynecology. Andrology. Obstetrics; Hematology; Humans; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Internal Medicine; Lymphatic Metastasis; Lymphatic system; Mammary gland diseases; MAP Kinase Signaling System - genetics; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Morpholines - pharmacology; Oncology; Pharmacology. Drug treatments; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Review; Signal Transduction; Tumor Cells, Cultured; Tumors; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor C - genetics; Vascular Endothelial Growth Factor C - metabolism
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-011-1049-2

Objective To investigate the signaling pathways involved in insulin-like growth factor-1 (IGF-1)-induced vascular endothelial growth factor C (VEGF-C) up-regulation and lymphatic metastasis in MDA-MB-231 breast cancer cells. Methods MDA-MB-231 breast cancer cells were exposed to IGF-1 with various concentrations. The expression level of VEGF-C was assessed by real-time PCR and Western blot. Akt and ERK1/2 phosphorylation was detected by Western blot. Signaling transduction inhibitors, LY294002 and PD98059, were used to block PI3K/Akt and MAPK/ERK1/2 signaling pathways, respectively. Results IGF-1 increased the level of VEGF-C expression in a dose-dependent manner in MDA-MB-231 breast cancer cells. In addition, phosphorylation of Akt and ERK1/2 was enhanced by IGF-1. Remarkably, inhibition of Akt phosphorylation by LY294002 completely blocked the effects on IGF-1-induced VEGF-C up-regulation. Inhibition of ERK1/2 phosphorylation by PD98059 reduced IGF-1-induced VEGF-C expression. Conclusion This study identified that PI3K/Akt and MAPK/ERK1/2 signaling pathways were involved in IGF-1-induced VEGF-C up-regulation and suggested their important roles in lymphatic metastasis in breast cancer.