Disabling of the erbB pathway followed by IFN-gamma modifies phenotype and enhances genotoxic eradication of breast tumors Journal Article
| Authors: | Nagai, Y.; Tsuchiya, H.; Runkle, E. A.; Young, P. D.; Ji, M. Q.; Norton, L.; Drebin, J. A.; Zhang, H.; Greene, M. I. |
| Article Title: | Disabling of the erbB pathway followed by IFN-gamma modifies phenotype and enhances genotoxic eradication of breast tumors |
| Abstract: | Reversion of the malignant phenotype of erbB2-transformed cells can be driven by anti-erbB2/neu monoclonal antibodies (mAbs), which disrupt the receptor's kinase activity. We examined the biologic effects of IFN-γ alone or after anti-erbB2/neu mAb treatment of erbB2-positive cells. IFN-γ had no effect on its own. Treatment of the tumors with anti-erbB2/neu mAbs followed by IFN-γ led to dramatic inhibition of tumor growth in vitro and in vivo with minimal mAb dosing. Sequential therapy enhanced the effects of chemotherapy. Moreover, IFN-γ with mAb treatment of mice with IFNγR knockdown tumors did not demonstrate marked synergistic eradication effects, indicating an unexpected role of IFN-γ on the tumor itself. Additionally, mAb and IFN-γ treatment also induced immune host responses that enhanced tumor eradication. Biochemical analyses identified loss of Snail expression in tumor cells, reflecting diminution of tumor-stem-cell-like properties as a consequence of altered activity of GSK3-β and KLF molecules. © 2015 The Authors. |
| Keywords: | signal transduction; protein expression; human cell; nonhuman; animal cell; mouse; phenotype; protein depletion; epidermal growth factor receptor 2; animal experiment; animal model; in vivo study; in vitro study; monoclonal antibody; cancer inhibition; immune response; gamma interferon; breast tumor; glycogen synthase kinase 3beta; cancer stem cell; tumor cell; molecular biology; transcription factor snail; protein modification; genotoxicity; kruppel like factor 4; biochemical analysis; gamma interferon receptor; human; female; priority journal; article |
| Journal Title: | Cell Reports |
| Volume: | 12 |
| Issue: | 12 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2015-09-29 |
| Start Page: | 2049 |
| End Page: | 2059 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2015.08.044 |
| PROVIDER: | scopus |
| PMCID: | PMC4591220 |
| PUBMED: | 26365188 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
