دورية أكاديمية
Mechanism of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells
| العنوان: | Mechanism of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells |
|---|---|
| المؤلفون: | Van Den Berg, Carla |
| المساهمون: | COLORADO UNIV HEALTH SCIENCES CENTER DENVER |
| المصدر: | DTIC AND NTIS |
| سنة النشر: | 2000 |
| المجموعة: | Defense Technical Information Center: DTIC Technical Reports database |
| مصطلحات موضوعية: | Biochemistry, Medicine and Medical Research, CELLS(BIOLOGY), BREAST CANCER, ULTRAVIOLET RADIATION, IRRADIATION, DRUGS, DEATH, CHEMOTHERAPY, INSULIN, PHOSPHORUS TRANSFERASES, TRANSFECTION, PI3K(PHOSPHATIDYLINOSITOL 3-KINASE), IGF-I(INSULIN-LIKE GROWTH FACTOR-I) |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://www.dtic.mil/docs/citations/ADA385739Test |
| الإتاحة: | http://www.dtic.mil/docs/citations/ADA385739Test http://oai.dtic.mil/oai/oai?&verb=getRecord&metadataPrefix=html&identifier=ADA385739Test |
| حقوق: | APPROVED FOR PUBLIC RELEASE |
| رقم الانضمام: | edsbas.3E2987EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |