Other
14 Authors
- Willmarth NE,
- Katiyar S,
- Casimiro MC,
- Ju X,
- Sakamaki T,
- Liu M,
- Popov VM,
- Joyce D,
- Yu Z,
- Jiao X,
- Wu K,
- Wang C,
- Ojeifo J,
- Pestell RG
| First Author | Liu M | Year | 2009 |
| Journal | Am J Pathol | Volume | 174 |
| Issue | 5 | Pages | 1910-20 |
| PubMed ID | 19349372 | Mgi Jnum | J:147968 |
| Mgi Id | MGI:3843104 | Doi | 10.2353/ajpath.2009.080706 |
| Citation | Liu M, et al. (2009) Nuclear factor-kappaB enhances ErbB2-induced mammary tumorigenesis and neoangiogenesis in vivo. Am J Pathol 174(5):1910-20 |
| abstractText | The (HER2/Neu) ErbB2 oncogene is commonly overexpressed in human breast cancer and is sufficient for mammary tumorigenesis in transgenic mice. Nuclear factor (NF)-kappaB activity is increased in both human and murine breast tumors. The immune response to mammary tumorigenesis may regulate tumor progression. The role of endogenous mammary epithelial cell NF-kappaB had not previously been determined in immune-competent animals. Furthermore, the role of the NF-kappaB components, p50 and p65, in tumor growth was not known. Herein, the expression of a stabilized form of the NF-kappaB-inhibiting IkappaBalpha protein (IkappaBalphaSR) in breast tumor cell lines that express oncogenic ErbB2 inhibited DNA synthesis and growth in both two- and three-dimensional cultures. Either NF-kappaB inhibition or selective silencing of p50 or p65 led to a loss of contact-independent tumor growth in vitro. IkappaBalphaSR reversed the features of the oncogene-induced phenotype under three-dimensional growth conditions. The NF-kappaB blockade inhibited ErbB2-induced mammary tumor growth in both immune-competent and immune-deficient mice. These findings were associated with both reduced tumor microvascular density and a reduction in the amount of vascular endothelial growth factor. The expression of IkappaBalphaSR in breast cancer tumors inhibited angiogenesis. Thus, mammary epithelial cell NF-kappaB activity enhances ErbB2-mediated mammary tumorigenesis in vivo by promoting both growth and survival signaling via the promotion of tumor vasculogenesis. |
