| First Author | Liu M | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 24 | Pages | 10464-73 |
| PubMed ID | 21159656 | Mgi Jnum | J:167597 |
| Mgi Id | MGI:4868625 | Doi | 10.1158/0008-5472.CAN-10-0732 |
| Citation | Liu M, et al. (2010) The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion. Cancer Res 70(24):10464-73 |
| abstractText | The role of mammary epithelial cell (MEC) NF-kappaB in tumor progression in vivo is unknown, as murine NF-kappaB components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-kappaB inhibitors block both tumor-associated macrophages (TAM) and MEC NF-kappaB, the importance of MEC NF-kappaB to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-kappaB (IkappaBalphaSR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-kappaB in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-kappaB enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IkappaBalphaSR inhibited tumor stem cell pathways. IkappaBalphaSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-kappaB contributes to mammary tumorigenesis. As we show that NF-kappaB contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-kappaB-dependent mammary tumorigenesis. |
