The role of the insulin-like growth factor-1 system in breast cancer

Abstract

IGF-1 is a potent mitogen of major importance in the mammary gland. IGF-1 binding to the cognate receptor, IGF-1R, triggers a signaling cascade leading to proliferative and anti-apoptotic events. Although many of the relevant molecular pathways and intracellular cascades remain to be elucidated, a growing body of evidence points to the important role of the IGF-1 system in breast cancer development, progression and metastasis. IGF-1 is a point of convergence for major signaling pathways implicated in breast cancer growth. In this review, we provide an overview and concise update on the function and regulation of IGF-1 as well as the role it plays in breast malignancies.

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

“…According to the literatures, Insulin‐like growth factors (IGFs) stimulated cell proliferation by activated MAPK, Akt 31 and S1P have been found to inhibit keratinocyte proliferation through inhibit Akt/PKB pathway induced by Insulin‐like growth factor I (IGF‐I) 32. In the cancer condition, triple negative breast cancer was reported to express high level of IGF‐I 31, 33. Therefore, S1P/S1PR1 signaling might downregulate IGF‐1/Akt/PKB axis to suppress cell proliferation.…”

Circulating concentrations of insulin like growth factor-1 in female dogs with spontane-ous mammary tumours

“…IGF-1 is one of the most potent mitogens for normal mammary epithelial cells and breast cancer cells (10,30) and mediates in survival and transformation, key factors affecting tumour development (1,10). There is evidence indicating that IGF-1 is a potent inhibitor of apoptosis, including that induced by cytotoxic chemotherapeutic agents (30), and regulates the expression of numerous genes implicated in breast tumorigenesis (1).…”

“…There is evidence indicating that IGF-1 is a potent inhibitor of apoptosis, including that induced by cytotoxic chemotherapeutic agents (30), and regulates the expression of numerous genes implicated in breast tumorigenesis (1). Studies have demonstrated that IGF-1 stimulates angiogenesis via up-regulation of VEGF and COX-2 (20), and plays a role in cell-cell adhesion and cell migration, promoting invasion and metastasis (24,28).…”

“…Moreover, some studies suggest IGF-1 has a role in cell-cell adhesion and cell migration (28). It is thought that these features can promote the development and progression of neoplasms (1,10). In humans the role of IGF-1 in tumorigenesis has been investigated intensively.…”

“…It is well known that GH/IGF-1 axis plays a fundamental role in the development of the human breast (22) and canine mammary gland (14), but is also involved in various neoplastic processes (17,24) including breast cancer (1,10). IGF-1 is a potent mitogenic and anti-apoptotic agent (30), which is also involved in angiogenesis stimulation (2,20).…”