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| Item Type: | Article |
|---|---|
| Title: | Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations |
| Creators Name: | Jing, H., Kase, J., Dörr, J.R., Milanovic, M., Lenze, D., Grau, M., Beuster, G., Ji, S., Reimann, M., Lenz, P., Hummel, M., Doerken, B., Lenz, G., Scheidereit, C., Schmitt, C.A. and Lee, S. |
| Abstract: | In malignancies, enhanced nuclear factor-{kappa}B (NF-{kappa}B) activity is largely viewed as an oncogenic property that also confers resistance to chemotherapy. Recently, NF-{kappa}B has been postulated to participate in a senescence-associated and possibly senescence-reinforcing cytokine response, thereby suggesting a tumor-restraining role for NF-{kappa}B. Using a mouse lymphoma model and analyzing transcriptome and clinical data from lymphoma patients, we show here that therapy-induced senescence presents with and depends on active NF-{kappa}B signaling, whereas NF-{kappa}B simultaneously promotes resistance to apoptosis. Further characterization and genetic engineering of primary mouse lymphomas according to distinct NF-{kappa}B-related oncogenic networks reminiscent of diffuse large B-cell lymphoma (DLBCL) subtypes guided us to identify Bcl2-overexpressing germinal center B-cell-like (GCB) DLBCL as a clinically relevant subgroup with significantly superior outcome when NF-κB is hyperactive. Our data illustrate the power of cross-species investigations to functionally test genetic mechanisms in transgenic mouse tumors that recapitulate distinct features of the corresponding human entity, and to ultimately use the mouse model-derived genetic information to redefine novel, clinically relevant patient subcohorts. |
| Keywords: | Cancer Therapy, Cellular Senescence, DLBCL, Lymphoma, Mouse Models, NF-{kappa}B, Antineoplastic Agents, Cell Aging, Tumor Cell Line, Cell Survival, Neoplastic Gene Expression Regulation, B-Cell Lymphoma, Large B-Cell Lymphoma, Non-Hodgkin Lymphoma, NF-kappa B, Signal Transduction, Animals, Mice |
| Source: | Genes & Development |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Volume: | 25 |
| Number: | 20 |
| Page Range: | 2137-2146 |
| Date: | 15 October 2011 |
| Official Publication: | https://doi.org/10.1101/gad.17620611 |
| PubMed: | View item in PubMed |
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