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

Paolo Ciana, Antonino Neri, Catarina Cappellini, Federica Cavallo, Mauro Pomati, Chih Chao Chang, Anna Teresa Maiolo, Luigia Lombardi

Research output: Contribution to journalArticle

Abstract

The NFKB-2 (Lyt-10) gene codes for an NF-κ-B-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-1OCα 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-1OCα 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-10Cα-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 NFKB2-p52-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.

Original languageEnglish
Pages (from-to)1805-1810
Number of pages6
JournalOncogene
Volume14
Issue number15
Publication statusPublished - 1997

Fingerprint

Lymphoma
Fibroblasts
Proteins
Ankyrins
Cell Line
Neoplasms
SCID Mice
Genes
Agar
Organism Cloning
Transcription Factors
Complementary DNA
Clone Cells
Phenotype
Skin
Injections

Keywords

  • NF-κB
  • NFKB-2
  • Transcription factor
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ciana, P., Neri, A., Cappellini, C., Cavallo, F., Pomati, M., Chang, C. C., ... Lombardi, L. (1997). Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts. Oncogene, 14(15), 1805-1810.

Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts. / Ciana, Paolo; Neri, Antonino; Cappellini, Catarina; Cavallo, Federica; Pomati, Mauro; Chang, Chih Chao; Maiolo, Anna Teresa; Lombardi, Luigia.

In: Oncogene, Vol. 14, No. 15, 1997, p. 1805-1810.

Research output: Contribution to journalArticle

Ciana, P, Neri, A, Cappellini, C, Cavallo, F, Pomati, M, Chang, CC, Maiolo, AT & Lombardi, L 1997, 'Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts', Oncogene, vol. 14, no. 15, pp. 1805-1810.
Ciana, Paolo ; Neri, Antonino ; Cappellini, Catarina ; Cavallo, Federica ; Pomati, Mauro ; Chang, Chih Chao ; Maiolo, Anna Teresa ; Lombardi, Luigia. / Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts. In: Oncogene. 1997 ; Vol. 14, No. 15. pp. 1805-1810.
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