IGF-IR Signaling in Breast Cancer.
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA355184
Entities
People
- Ewa Surmacz
Organizations
- Thomas Jefferson University