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 language | English |
|---|---|
| Pages (from-to) | 1805-1810 |
| Number of pages | 6 |
| Journal | Oncogene |
| Volume | 14 |
| Issue number | 15 |
| Publication status | Published - 1997 |
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Keywords
- NF-κB
- NFKB-2
- Transcription factor
- Transformation
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts
AU - Ciana, Paolo
AU - Neri, Antonino
AU - Cappellini, Catarina
AU - Cavallo, Federica
AU - Pomati, Mauro
AU - Chang, Chih Chao
AU - Maiolo, Anna Teresa
AU - Lombardi, Luigia
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - NF-κB
KW - NFKB-2
KW - Transcription factor
KW - Transformation
UR - http://www.scopus.com/inward/record.url?scp=0031009479&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031009479&partnerID=8YFLogxK
M3 - Article
C2 - 9150386
AN - SCOPUS:0031009479
VL - 14
SP - 1805
EP - 1810
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 15
ER -