Mechanism of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells
Abstract
Upregulation of IGF-I (Insulin-like Growth Factor-I) receptor dependent pathways like phosphatidylinositol 3-kinase (PI3K) may diminish chemosensitivity of breast cancer cells via c-Jun N-terminal kinase (JNK) response. In this project we set out to determine if IGF-I activates the PI3K survival pathway. We also predicted that IGF-I treatment of breast cancer cells would inhibit the stress-induced pathway JNK which is activated by some chemotherapy drugs. Initially, we performed PI3K assays and determined that IGF-I treatment of MCF-7 breast cancer cells strongly activated PI3K. Similarly, IGF-I treatment activated both downstream kinases Akt and p70S6. Next, we assessed if JNK activity was induced by stress treatment of MCF-7 cells, using doxorubicin, taxol, taxotere, and ultraviolet irradiation (UV). Taxol, taxotere and UV were the strongest activators of JNK activity and were used for subsequent IGF-I co-treatment assays. Surprisingly, IGF-I treatment alone lead to significant activation of JNK. Further, inhibition of PI3K inhibited IGF-I induction of JNK, suggesting that PI3-kinase may convey survival responses through JNK. When cells were co-treated with IGF-I and stress treatment, JNK activity was additive compared to either treatment alone. Transfection experiments support that IGF-I mediated survival responses are conveyed through PI3K and Akt.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385739
Entities
People
- Carla Van Den Berg
Organizations
- University of Colorado Health