Regulation of axin2 expression at the levels of transcription, translation and protein stability in lung and colon cancer.
Axin2 is a negative regulator of Wnt/beta-catenin signalling with a role in tumour suppression. Its expression can be up-regulated by E2F1 allowing cross-talk between the pRb/E2F and Wnt/beta-catenin pathways, which both have critical roles in the development of many cancers. Thereby, axin2 may have a crucial role in carcinogenesis and here we examine the regulation of its expression. Axin2 mRNAs contain one of three different 5' untranslated regions that can have profound effects on the efficiency of axin2 translation. We show that axin2 mRNA expression is altered in tumours at levels of both total mRNA and relative proportions of alternative 5' untranslated regions. Moreover, the translational efficiencies defined by these 5' untranslated regions are modulated considerably. Additionally, we show that stability of axin2 protein provides a further level of expression regulation. We discuss this complex regulation in terms of axin2's function in carcinogenesis.
Hughes
Thomas A
TA
Camelia Botnar Laboratories, Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. t.hughes@ich.ucl.ac.uk
Brady
Hugh J M
HJ
D020121:5' Untranslated Regions; D060466:Axin Protein; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; C491761:AXIN2 protein, human; D060466:Axin Protein; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger