IGF-IR Signaling in Breast Cancer.
Annual rept. 15 Aug 97-14 Aug 98
THOMAS JEFFERSON UNIV PHILADELPHIA PA
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Clinical and experimental evidence suggest that the insulin-like growth factor receptor IGF-IR is involved in breast cancer etiology. For instance, IGF-IR is overexpressed in breast tumors relative to normal breast epithelium and high levels of IGF-I an IGF-IR ligand correlate with breast cancer risk in premenopausal women. In vitro, IGF-IR regulates the growth and survival of breast cancer cells and plays a role in the development of estrogen-independence. Antiestrogens inhibit IGF-I- dependent growth by interfering with IGF-IR signaling. The mechanisms of this interference are not clear. Here we discuss the evidence that a pure antiestrogen ICI 182,780 specifically blocks breast cancer growth through downregulation of the expression of IRS-i, a major IGF signaling intermediate, Although the role of IGF-IR is breast cancer cell proliferation is clear, its function in growth-unrelated processes, such as cell adhesion, migration and metastasis is less well understood. Here, we report that an IGF-IR signaling substrate SHC, through its dynamic interactions with alpha5beta1integrin a fibronectin receptor participates in the regulation of breast cancer cell adhesion and motility.
- Anatomy and Physiology
- Medicine and Medical Research