Overexpressed max is not oncogenic and attenuates myc-induced lymphoproliferation and lymphomagenesis in transgenic mice.
The cellular growth promoting function of the Myc oncoprotein requires its heterodimerization with the Max protein, but Max can also form complexes that inhibit Myc action. To determine whether max overexpression in vivo is oncogenic and whether it can modulate the action of Myc, we generated transgenic mice in which the max gene was directed to express in lymphoid cells by a linked immunoglobulin heavy chain enhancer (E mu). Expression of the transgene at substantially higher levels than the endogenous max gene did not perturb lymphoid homeostasis in adult animals nor predispose to lymphomagenesis. The numbers of B-lymphoid cells in very young animals were reduced. Moreover, analysis of bi-transgenic E mu-myc/E mu-max mice revealed that max overexpression attenuated the premalignant B-lymphoproliferative state induced by an E mu-myc transgene and reduced the rate of lymphoma onset. These results suggest that elevation of Max expression in vivo inhibits the function of Myc.
Lindeman
G J
GJ
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Australia.
Harris
A W
AW
Bath
M L
ML
Eisenman
R N
RN
Adams
J M
JM
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D016259:Genes, myc; D006410:Hematopoiesis; D006706:Homeostasis; D008223:Lymphoma / Q000209:etiology* / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D014157:Transcription Factors; C068422:Max protein, mouse