IGF-IR Signaling in Breast Cancer
Abstract
The insulin-like growth factor I receptor (IGF-IR) is a multifunctional tyrosine kinase that has been implicated in breast cancer. The IGF-IR is often overexpressed in ER-positive breast tumors and this feature predicts tumor drug and radioresistance and cancer recurrence at the primary site. Over the period 1996-2000, we studied IGF-IR signaling pathways that may contribute to breast cancer development and progression. We developed different cell lines with either overexpression or downregulation of the IGF-IR or its major signaling substrates. Using these model systems, we characterized cross-talk between estrogen receptor and IGF-IR signaling, and we provided the first evidence that the IGF-IR, especially the IGF-IR/IRS- l/PI-3K pathway, plays a major role in 2 processes involved in cancer progression: antiestrogen-resistance and estrogen%independence. We also described, for the first time, interactions between the IGF-IR and cell-cell (cadherins and catenins) and cell-substrate (integrins) systems. Our data indicated that the IGF-I signal can increase cell adhesion and motility, the functions that are critical for metastatic cell spread. Recently, we demonstrated that in ER-negative metastatic cells, IGF-1-induced motility is mediated through PI-3 and p38 kinases, and is inhibited by the activation of ERKl/ERK2 kinases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA384240
Entities
People
- Ewa Surmacz
Organizations
- Thomas Jefferson University