Mechanism of Growth Factor Attenuation of Cell Death in Chemotheraphy Treated Breast Cancer Cells.

摘要

Upregulation of IGF-I (Insulin-like Growth Factor) receptor dependent pathways like phosphatidylinositol 3-kinase (PI 3-kinase) may diminish chemosensitivity of breast cancer cells via c- Jun N-terminal Kinase (JNK) response. In this project we have determined that IGF-I activates the survival pathway involving PI 3-kinase and Akt. Using stable transfection approaches we have confirmed the survival effect of activated Aict in MCF-7 cells. Surprisingly, we have also observed that IGF-I induces JNK in breast cancer cells. IGF-I and chemotherapy co-treatment results in additive effect on JNK activity, in contrast to our predicted results that IGF-I would antagonize chemotherapy induced JNK activity. PI 3-kinase mediates IGF-I induction of JNK in MCF-7 cells but not in T47D cells. We plan to further confirm the importance of JNK in IGF-I mediated survival effects in breast cancer cells.