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Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice. Cancer Res 2005 Sep 01;65(17):7644-52

Date

09/06/2005

Pubmed ID

16140930

DOI

10.1158/0008-5472.CAN-05-1222

Scopus ID

2-s2.0-24744440161   20 Citations

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.

Author List

Park SS, Shaffer AL, Kim JS, duBois W, Potter M, Staudt LM, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Animals
Gene Expression
Genes, Immunoglobulin
Genes, myc
Lymphoid Tissue
Mice
Mice, Inbred BALB C
Mice, Transgenic
Peritoneal Neoplasms
Plasmacytoma
Precancerous Conditions
Transgenes