التفاصيل البيبلوغرافية
| العنوان: |
Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models |
| المؤلفون: |
Valentina D’Amato, Sarah J. Parsons, Giancarlo Troncone, Sabino De Placido, Vincenzo Damiano, Lucia Raimondo, Bianca Maria Veneziani, Roberto Bianco, Lucia Nappi, Francesca Iommelli, C. D'Amato, Roberta Marciano, Luigi Formisano, Roberta De Rosa, Antonella Scorziello |
| المساهمون: |
Formisano, L, Nappi, L, Rosa, R, Marciano, R, D., Amato C, D., Amato V, Damiano, V, Raimondo, L, Iommelli, F, Scorziello, Antonella, Troncone, Giancarlo, Veneziani, BIANCA MARIA, Parsons, Sj, DE PLACIDO, Sabino, Bianco, Roberto |
| المصدر: |
Breast Cancer Research : BCR |
| بيانات النشر: |
Springer Science and Business Media LLC, 2014. |
| سنة النشر: |
2014 |
| مصطلحات موضوعية: |
Lung Neoplasms, Receptor, ErbB-2, Metastasis, Mice, Cell Movement, cetuximab, Antineoplastic Combined Chemotherapy Protocols, Epidermal growth factor receptor, Enzyme Inhibitors, RNA, Small Interfering, skin and connective tissue diseases, Medicine(all), Mice, Inbred BALB C, biology, Drug Synergism, ErbB Receptors, src-Family Kinases, Female, RNA Interference, Signal transduction, Tyrosine kinase, Research Article, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, medicine.drug, Cell Survival, Transplantation, Heterologous, Mice, Nude, Antineoplastic Agents, Breast Neoplasms, Lapatinib, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Benzodioxoles, Protein Kinase Inhibitors, Cell Proliferation, Epidermal Growth Factor, Cell growth, Cancer, medicine.disease, Enzyme Activation, Drug Resistance, Neoplasm, Quinazolines, Cancer research, biology.protein, saracatinib, Neoplasm Transplantation |
| الوصف: |
Introduction: Src tyrosine kinase overactivation has been correlated with a poor response to human epidermal growth factor receptor 2 (HER2) inhibitors in breast cancer. To identify the mechanism by which Src overexpression sustains this resistance, we tested a panel of breast cancer cell lines either sensitive or resistant to lapatinib.Methods: To determine the role of Src in lapatinib resistance, we evaluated the effects of Src inhibition/silencing in vitro on survival, migration, and invasion of lapatinib-resistant cells. In vivo experiments were performed in JIMT-1 lapatinib-resistant cells orthotopically implanted in nude mice. We used artificial metastasis assays to evaluate the effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Src-dependent signal transduction was investigated with Western blot and ELISA analyses.Results: Src activation was higher in lapatinib-resistant than in lapatinib-sensitive cells. The selective small-molecule Src inhibitor saracatinib combined with lapatinib synergistically inhibited the proliferation, migration, and invasion of lapatinib-resistant cells. Saracatinib combined with lapatinib significantly prolonged survival of JIMT-1-xenografted mice compared with saracatinib alone, and impaired the formation of lung metastases. Unexpectedly, in lapatinib-resistant cells, Src preferentially interacted with epidermal growth factor receptor (EGFR) rather than with HER2. Moreover, EGFR targeting and lapatinib synergistically inhibited survival, migration, and invasion of resistant cells, thereby counteracting Src-mediated resistance. These findings demonstrate that Src activation in lapatinib-resistant cells depends on EGFR-dependent rather than on HER2-dependent signaling.Conclusions: Complete pharmacologic EGFR/HER2 inhibition is required to reverse Src-dependent resistance to lapatinib in breast cancer. © 2014 Formisano et al.; licensee BioMed Central Ltd. |
| تدمد: |
1465-542X |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::797ee0548ff2209573b79e6733ab78f2Test
https://doi.org/10.1186/bcr3650Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....797ee0548ff2209573b79e6733ab78f2 |
| قاعدة البيانات: |
OpenAIRE |
