Aarhus University Seal / Aarhus Universitets segl

Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus. / Rasmussen, Mads Heilskov; Sørensen, Annette Balle; Morris, D W; Dutra, J C; Engelhard, E K; Wang, C L; Schmidt, J; Pedersen, Finn Skou.

I: Virology, Bind 337, Nr. 2, 2005, s. 353-64.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Rasmussen, Mads Heilskov ; Sørensen, Annette Balle ; Morris, D W ; Dutra, J C ; Engelhard, E K ; Wang, C L ; Schmidt, J ; Pedersen, Finn Skou. / Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus. I: Virology. 2005 ; Bind 337, Nr. 2. s. 353-64.

Bibtex

@article{63cfd2707b2a11ddb7fc000ea68e967b,
title = "Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.",
abstract = "Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.",
keywords = "3T3 Cells, Animals, Basic-Leucine Zipper Transcription Factors, DNA, Neoplasm, Disease Models, Animal, Genes, fos, Leukemia Virus, Murine, Lymphoma, B-Cell, Mice, Mice, Inbred Strains, Mutagenesis, Insertional, Polymerase Chain Reaction, Proviruses, RNA, Messenger, RNA, Viral, Repressor Proteins, Retroviridae, Thymus Gland, Transcription Factors, Tumor Cells, Cultured, Virus Latency",
author = "Rasmussen, {Mads Heilskov} and S{\o}rensen, {Annette Balle} and Morris, {D W} and Dutra, {J C} and Engelhard, {E K} and Wang, {C L} and J Schmidt and Pedersen, {Finn Skou}",
year = "2005",
doi = "10.1016/j.virol.2005.04.027",
language = "English",
volume = "337",
pages = "353--64",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press",
number = "2",

}

RIS

TY - JOUR

T1 - Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.

AU - Rasmussen, Mads Heilskov

AU - Sørensen, Annette Balle

AU - Morris, D W

AU - Dutra, J C

AU - Engelhard, E K

AU - Wang, C L

AU - Schmidt, J

AU - Pedersen, Finn Skou

PY - 2005

Y1 - 2005

N2 - Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.

AB - Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.

KW - 3T3 Cells

KW - Animals

KW - Basic-Leucine Zipper Transcription Factors

KW - DNA, Neoplasm

KW - Disease Models, Animal

KW - Genes, fos

KW - Leukemia Virus, Murine

KW - Lymphoma, B-Cell

KW - Mice

KW - Mice, Inbred Strains

KW - Mutagenesis, Insertional

KW - Polymerase Chain Reaction

KW - Proviruses

KW - RNA, Messenger

KW - RNA, Viral

KW - Repressor Proteins

KW - Retroviridae

KW - Thymus Gland

KW - Transcription Factors

KW - Tumor Cells, Cultured

KW - Virus Latency

U2 - 10.1016/j.virol.2005.04.027

DO - 10.1016/j.virol.2005.04.027

M3 - Journal article

C2 - 15913695

VL - 337

SP - 353

EP - 364

JO - Virology

JF - Virology

SN - 0042-6822

IS - 2

ER -