Mechanisms of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells
Abstract
IOF-I receptor (IGF-IR) overexpression is a frequent aberration in found in breast tumors. ICIF-IR activation may serve its greatest purpose in cancer cells by activating intracellular PI 3 -kinase and its downstream target Akt to convey proliferation and survival of breast cancer cells. In breast cancer cell lines, treatment with IGF-I results in ICIF-IR activation and tyrosine phosphorylation of the IRS-I docking protein. The p85 subunit of PI 3-kinase then binds to IRS-I to activate downstream kinases such as Akt and p7O56 kinase. IGF-IR is an important target for development of new breast cancer interventions since its expression has been observed in 87% of breast cancer specimens. Breast cancer cells expressing IGF-IR undergo a robust proliferative response when exposed to the receptor's ligands. A great amount of research has focused on the effect of growth factor activation of Akt on breast cancer cell survival, with the belief that Akt must convey the majority of PI 3-kinase effects. My lab has studied the survival responses induced by IGF-I treatment of breast cancer cells and how these responses may be altered by cellular stress, including chemotherapy and radiation treatment induction of the p53 tumor suppressor protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA409432
Entities
People
- Carla Van Den Berg
Organizations
- University of Colorado Boulder