Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts

Oncogene. 1997 Apr 17;14(15):1805-10. doi: 10.1038/sj.onc.1201015.


The NFKB-2 (Lyt-10) gene codes for an NF-kappaB-related transcription factor containing rel-polyG-ankyrin domains. Rearrangements of the NFKB-2 locus leading to the production of 3' truncated NFKB-2 proteins are recurrently found in lymphoid neoplasms, particularly cutaneous lymphomas. Such mutant NFKB-2 proteins have lost the ability to repress transcription that is typical of NFKB-2 subunit p52, and function as constitutive transcriptional activators. To verify whether the expression of abnormal NFKB-2 proteins can lead to malignant transformations in mammalian cells, we transfected human lymphoblastoid cell lines and murine fibroblasts (Balb/3T3) with expression vectors carrying the cDNAs coding for normal NFKB-2p52, Lyt-10C alpha or LB40 proteins, which are representative of the abnormal types found in lymphoma cases. The expression of both normal and mutant NFKB-2 proteins has a lethal effect on lymphoblastoid cells and a cytotoxic effect was also observed in murine fibroblasts. The fibroblast cell lines expressing Lyt-10C alpha or LB40, but not those expressing normal NFKB-2p52, were capable of forming colonies in soft agar. The analysis of individual clones revealed that cloning efficiency correlated with the expression levels of the abnormal proteins. 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. Our results show that mutant NFKB-2 proteins can lead to the transformed phenotype, and support the hypothesis that alterations in NFKB-2 genes may play a role in lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / cytology
  • 3T3 Cells / drug effects*
  • 3T3 Cells / physiology
  • Animals
  • Cell Transformation, Neoplastic* / drug effects
  • Female
  • Humans
  • Lymphoma / genetics
  • Lymphoma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mutation
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • NF-kappa B p52 Subunit
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*


  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Neoplasm Proteins
  • Proto-Oncogene Proteins