Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer
| Autor: | Richard J. Pietras, Yanyuan Wu, Jaydutt V. Vadgama, Rudy Sanchez, Kay Foos, Nalo Hamilton, David Austin, Brittney Chau, Diana C. Márquez-Garbán |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Triple Negative Breast Neoplasms Pharmacology triple-negative breast cancer insulin-like growth factor-2 androgen receptor BMS-754807 NVP-AEW541 enzalutamide IGF1R/IR inhibition IGF2 signaling AKT kinase apoptosis Receptor IGF Type 1 lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine IGF1R Antineoplastic Combined Chemotherapy Protocols 2.1 Biological and endogenous factors Molecular Targeted Therapy Aetiology Receptor lcsh:QH301-705.5 Spectroscopy Triple-negative breast cancer Cancer Tumor Triazines General Medicine IR inhibition 3. Good health Computer Science Applications 030220 oncology & carcinogenesis Benzamides Androgens Female Signal Transduction Cell Survival Antineoplastic Agents Biology Catalysis Article Cell Line Inorganic Chemistry 03 medical and health sciences Breast cancer Insulin-Like Growth Factor II Cell Line Tumor Breast Cancer Nitriles Phenylthiohydantoin medicine Genetics Enzalutamide Humans Pyrroles IGF Type 1 Physical and Theoretical Chemistry Molecular Biology Insulin-like growth factor 1 receptor Cell Proliferation Chemical Physics Cell growth Organic Chemistry Androgen Antagonists medicine.disease Androgen receptor 030104 developmental biology Pyrimidines chemistry lcsh:Biology (General) lcsh:QD1-999 Apoptosis Cancer research Pyrazoles Other Biological Sciences Other Chemical Sciences |
| Zdroj: | International Journal of Molecular Sciences, Vol 18, Iss 11, p 2305 (2017) International Journal of Molecular Sciences; Volume 18; Issue 11; Pages: 2305 International journal of molecular sciences, vol 18, iss 11 International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2. Treatment with IGF2 stimulated cell proliferation in vitro (p < 0.05). Importantly, combination treatments with IGF1R inhibitors BMS-754807 and NVP-AEW541 elicited significant inhibition of TNBC cell proliferation (p < 0.001). Based on Annexin-V binding assays, BMS-754807, NVP-AEW541 and enzalutamide induced TNBC cell death (p < 0.005). Additionally, combination of enzalutamide with BMS-754807 or NVP-AEW541 exerted significant reductions in TNBC proliferation even in cells with low AR expression (p < 0.001). Notably, NVP-AEW541 and BMS-754807 reduced AR levels in BT549 TNBC cells. These results provide evidence that IGF2 promotes TNBC cell viability and proliferation, while inhibition of IGF1R/IR and AR pathways contribute to blockade of TNBC proliferation and promotion of apoptosis in vitro. |
| Databáze: | OpenAIRE |
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