Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Extraosseous IL-6 transgenic mouse plasmacytoma sometimes lacks Myc-activating chromosomal translocation. Genes Chromosomes Cancer 2005 Jun;43(2):137-46

Date

03/08/2005

Pubmed ID

15751044

DOI

10.1002/gcc.20172

Abstract

The cellular oncogene MYC and plasma cell growth, differentiation, and survival factor IL-6 play critical roles in the natural history of human plasma cell neoplasms such as multiple myeloma (MM). Myc and IL-6 also are at the center of neoplastic plasma cell transformation in BALB/c mice that carry a human IL-6 transgene and, therefore, predictably develop plasmacytomas (PCTs). We showed previously that, much like advanced MM or human myeloma cell lines (HMCLs), in which MYC is frequently deregulated in cis because of complex cytogenetic aberrations juxtaposing MYC to immunoglobulin enhancers, IL-6 transgenic PCTs commonly deregulate Myc in cis by chromosomal translocation, predominantly T(12;15)(Igh-Myc). In this article, we show that, analogous to primary MM in which MYC is mostly deregulated in trans by signaling pathways converging at the MYC promoter, IL-6 transgenic PCTs sometimes develop in the absence of Myc translocations, thus activating Myc in trans. We present cytogenetic and molecular evidence on two IL-6 transgenic PCTs that contained overexpressed Myc protein but lacked T(12;15)(Igh-Myc) and two related Myc--deregulating translocations that juxtapose Myc to immunoglobulin light-chain instead of heavy-chain enhancers: T(6;15)(Igkappa-Pvt1) and T(15;16)(Pvt1-Iglambda). We conclude that Myc translocations are not strictly required for IL-6-driven PCT development in mice. IL-6 transgenic PCTs may provide a valuable model system for elucidating both trans and cis mechanisms of Myc deregulation of great relevance for MYC deregulation in human MM.

Author List

McNeil N, Kim JS, Ried T, 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

Animals
Blotting, Southern
Genes, myc
In Situ Hybridization, Fluorescence
Interleukin-6
Karyotyping
Mice
Mice, Inbred BALB C
Mice, Transgenic
Plasmacytoma
Translocation, Genetic
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75