Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts
| Autor: | Anna Teresa Maiolo, Luigia Lombardi, Antonino Neri, Paolo Ciana, Federica Cavallo, M. Pomati, Chih Chao Chang, Catarina Cappellini |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Lymphoma Mutant Mice SCID Biology Mice NF-kappa B p52 Subunit Proto-Oncogene Proteins Gene expression Genetics medicine Animals Humans Cytotoxic T cell Fibroblast Molecular Biology Transcription factor Mice Inbred BALB C Expression vector NF-kappa B 3T3 Cells Transfection Molecular biology Neoplasm Proteins Cell Transformation Neoplastic medicine.anatomical_structure Cell culture Mutation Female |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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