Accession Number:

ADA355184

Title:

IGF-IR Signaling in Breast Cancer.

Descriptive Note:

Annual rept. 15 Aug 97-14 Aug 98

Corporate Author:

THOMAS JEFFERSON UNIV PHILADELPHIA PA

Personal Author(s):

Report Date:

1998-09-01

Pagination or Media Count:

68.0

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE