Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice

SUNG SUP PARK; Arthur L SHAFFER; JOONG SU KIM; Wendy DUBOIS; Michael POTTER; Louis M STAUDT; Siegfried JANZ

doi:10.1158/0008-5472.CAN-05-1222

Back

Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice

Journal article

Open access

Peer reviewed

Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice

SUNG SUP PARK, Arthur L SHAFFER, JOONG SU KIM, Wendy DUBOIS, Michael POTTER, Louis M STAUDT and Siegfried JANZ

Cancer research (Chicago, Ill.), Vol.65(17), pp.7644-7652

2005

DOI: 10.1158/0008-5472.CAN-05-1222

PMID: 16140930

Files and links (1)

url

https://doi.org/10.1158/0008-5472.CAN-05-1222View

Published (Version of record) Open Access

Abstract

Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carrying Myc(His) just 5' of the intronic heavy-chain enhancer Emu (strain iMyc(Emu)) provide a specific model of the type of T(12;15) found in a subset (approximately 20%) of plasmacytomas that develop "spontaneously" in the gut-associated lymphoid tissue (GALT) of interleukin-6 transgenic BALB/c (C) mice. Here we show that the transfer of the iMyc(Emu) transgene from a mixed genetic background of segregating C57BL/6 x 129/SvJ alleles to the background of C increased the incidence of GALT plasmacytomas by a factor of 2.5 in first-generation backcross mice (C.iMyc(Emu) N1). Third-generation backcross mice (C.iMyc(Emu) N3, approximately 94% C alleles) were hypersusceptible to inflammation-induced peritoneal plasmacytomas (tumor incidence, 100%; mean tumor onset, 86 +/- 28 days) compared with inbred C mice (tumor incidence, 5% on day 150 after tumor induction). Peritoneal plasmacytomas of C.iMyc(Emu) N3 mice overexpressed Myc(His), produced monoclonal immunoglobulin, and exhibited a unique plasma cell signature upon gene expression profiling on mouse Lymphochip cDNA microarrays. These findings indicated that the iMyc(Emu) transgene accelerates plasmacytoma development by collaborating with tumor susceptibility alleles of strain C and circumventing the requirement for tumor precursors to acquire deregulated Myc by chromosomal translocation.

Hematologic and hematopoietic diseases

Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis

Biological and medical sciences

Medical sciences

Details

Title: Subtitle: Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice
Creators: SUNG SUP PARK - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States
Arthur L SHAFFER - Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States
JOONG SU KIM - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States
Wendy DUBOIS - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States
Michael POTTER - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States
Louis M STAUDT - Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States
Siegfried JANZ - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.65(17), pp.7644-7652
DOI: 10.1158/0008-5472.CAN-05-1222
PMID: 16140930
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Publisher: American Association for Cancer Research
Language: English
Date published: 2005
Academic Unit: Pathology
Record Identifier: 9984083262602771

Metrics

19 Record Views

20 Times Cited - Web of Science