| First Author | Connelly L | Year | 2011 |
| Journal | Oncogene | Volume | 30 |
| Issue | 12 | Pages | 1402-12 |
| PubMed ID | 21076466 | Mgi Jnum | J:170777 |
| Mgi Id | MGI:4947336 | Doi | 10.1038/onc.2010.521 |
| Citation | Connelly L, et al. (2011) Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden. Oncogene 30(12):1402-12 |
| abstractText | The transcription factor nuclear factor kappa B (NF-kappaB) is activated in human breast cancer tissues and cell lines. However, it is unclear whether NF-kappaB activation is a consequence of tumor formation or a contributor to tumor development. We developed a doxycycline (dox)-inducible mouse model, termed DNMP, to inhibit NF-kappaB activity specifically within the mammary epithelium during tumor development in the polyoma middle T oncogene (PyVT) mouse mammary tumor model. DNMP females and PyVT littermate controls were treated with dox from 4 to 12 weeks of age. We observed an increase in tumor latency and a decrease in final tumor burden in DNMP mice compared with PyVT controls. A similar effect with treatment from 8 to 12 weeks indicates that outcome is independent of effects on postnatal virgin ductal development. In both cases, DNMP mice were less likely to develop lung metastases than controls. Treatment from 8 to 9 weeks was sufficient to impact primary tumor formation. Inhibition of NF-kappaB increases apoptosis in hyperplastic stages of tumor development and decreases proliferation at least in part by reducing Cyclin D1 expression. To test the therapeutic potential of NF-kappaB inhibition, we generated palpable tumors by orthotopic injection of PyVT cells and then treated systemically with the NF-kappaB inhibitor thymoquinone (TQ). TQ treatment resulted in a reduction in tumor volume and weight as compared with vehicle-treated control. These data indicate that epithelial NF-kappaB is an active contributor to tumor progression and demonstrate that inhibition of NF-kappaB could have a significant therapeutic impact even at later stages of mammary tumor progression. |
