Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

Molecular mechanisms of constitutive NF-κB/Rel activation in Hodgkin/Reed-Sternberg cells

“…In agreement with a recent publication (Wood et al, 1998), we did not detect full length IkBa protein in L428 or KMH-2 cells. Disruption of wild type IkBa (wtIkBa) expression in both cell lines resulted from point mutations, which cause expression of truncated IkBa (data not shown).…”

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

“…This latter model would be consistent with the complete loss of p100 NF-kB-2 seen in the HUT78 CTCL cells, as well as with the lymphoid hyperplasia observed in mice in which targeted gene deletions were performed to`knock-out' p100 while retaining p52 gene expression (Ishikawa et al, 1997). A model invoking loss of IkB-like activity would also be consistent with older reports that inhibition of IkBa by antisense approaches resulted in transformation of NIH3T3 cells (Beauparlant et al, 1994), and with reports of IkBa mutations in patients with Hodgkin's disease (Cabannes et al, 1999;Krappmann et al, 1999;Wood et al, 1998). This model is also reminiscent of one reported mechanism by which HTLV-1 Tax leads to increased NF-kB activity (Kanno et al, 1994).…”

Mutations in the NF-κB signaling pathway: implications for human disease

“…In several of these HL cells and perhaps as many as 10% of HL HRS cell biopsy samples, the lack of IkBa is due to loss-of-function mutations (e.g., small insertions, deletions or nonsense) in one allele of the IKBA gene couples with the deletion or inactivation of the second IKBA allele (Wood et al, 1998;Cabannes et al, 1999;Jungnickel et al, 2000;Emmerich et al, , 2003. As a consequence of the constitutive NF-kB signaling, several NF-kB target genes are overexpressed in HL cells, including ones encoding antiapoptotic proteins (such as A1, c-IAP2, TRAF1 and Bcl-X L ) and growth-promoting proteins (including cyclin D2, CD86 and CD40) (Hinz et al, 2001).…”