In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025).
To investigate the impact of non-canonical NF-κB signaling on lung carcinogenesis, we employed transgenic mice with doxycycline-inducible expression of p52 in airway epithelial cells. p52 over-expression led to increased tumor number and progression after injection of the carcinogen urethane.
We analysed several ligands and receptors of the alternative NF-κB pathway, RelB, p52 nuclear translocation and target genes in tissue samples of <i>H. pylori</i>-infected patients with different degrees of gastritis or early gastric tumours by in situ hybridisation, immunohistochemistry, Western blot and real-time PCR analyses.
Inhibiting RelB in aggressive androgen-independent PC-3 cells by stable or conditional expression of a dominant-negative p100 mutant significantly reduced the incidence and growth rate of tumors.
Consistent with activation of the non-canonical pathway, p52 and RelB co-localized in adenocarcinoma cells in sections of pancreatic tumor tissue, and each of the tumor cell lines displayed elevated p52 levels.
Injection of the Lyt-10C alpha-transfected Balb cells in SCID mice led to tumor formation in all of the animals, whereas no tumors were observed in the mice injected with control or NFKB-2p52-transfected cells, thus indicating that abnormal NFKB-2 protein expression is tumorigenic in vivo.
Overall, our results indicate that NFKB2 rearrangements in lymphoid neoplasia may occur by heterogeneous mechanisms, including internal chromosomal deletion or chromosomal translocation.