Cell-Cell Adhesion and Insulin-Like Growth Factor I Receptor in Breast Cancer.
Abstract
Disorganized epithelial tissue morphology is a prerequisite of breast tumor progression. Determining the mechanisms controlling cell-cell interactions will be a step towards the understanding how to prevent processes of tumor cell spreading, invasion and metastasis. Accumulating evidence suggests an important role of a natural modulator, such as insulin-like growth factor (IGF-1), and the pharmacological compounds, including antiestrogens, in regulating of E-cadherin-mediated intercellular adhesion in breast carcinomas. Molecular mechanisms, by which IGF-1 and antiestrogens modulate cell-cell associations, have not been clarified. In the present work, we investigated the functional role of different IGF-1 receptor (IGF-IR) domains in E-cadherin-mediated intercellular aggregation. The major achievement of this work is the development of the unique model consisting of MCF-7-derived human breast cancer cells, in which the normal IGF-IR is partially or completely inactivated by co-expression of its dominant-negative forms. Taking advantage of this model, we determined that IGF-IR catalytic activity and signaling mediated by the C-terminal region of the IGF-IR are critical for aggregation of MCF-7 breast cancer cells grown on the extracellular matrix. Additionally, we discovered that in MCF-7 cells, a non-steroidal antiestrogen Tamoxifen inhibited cell growth in monolayer and in three-dimensional culture; which was associated with blocked IGF-IR/IRS-1-mediated signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA365472
Entities
People
- Marina A. Guvakova
Organizations
- Thomas Jefferson University