As the proliferation promoter noradrenaline induces expression of ICER (induced cAMP early repressor) in proliferative brown adipocytes, ICER may not be a universal tumour suppressor.
The CREM (cAMP-response-element modulator) gene product ICER (induced cAMP early repressor) has been proposed to function as a tumour (cell proliferation) suppressor. To investigate the generality of this concept, the expression pattern of ICER in brown adipocytes was followed; this was critical because brown adipocytes are one of few cell types in which cAMP is associated positively with cell proliferation but negatively with apoptosis. In response to the physiological stimulus of cold (which induces cell proliferation), ICER mRNA levels were increased in brown adipose tissue in vivo. In brown adipocytes in primary culture, ICER gene expression was induced by noradrenaline (norepinephrine) not only in the mature state (where noradrenaline potentiates differentiation), but also in the proliferative state of the cell cultures (where noradrenaline enhances cell proliferation). The induction was mediated via beta-receptors and the cAMP/protein kinase A pathway. The induced ICER appeared to repress its own expression and that of the beta2-adrenoceptor. It is thus evident that also in cell types in which cAMP induces proliferation, and even when these cells are in the proliferative state, ICER expression is induced by the same agents that stimulate proliferation. This can either mean that ICER is not a general tumour suppressor, or that brown adipocytes temporally or spatially avoid this role of ICER.
Thonberg
H
H
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Lindgren
E M
EM
Nedergaard
J
J
Cannon
B
B
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D051786:Cyclic AMP Response Element Modulator; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D007700:Kinetics; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D009638:Norepinephrine