Regulatory region of metastasis-inducing DNA is the binding site for T cell factor-4.
Small 1000 bp fragments of DNA derived from human malignant breast cancer cells have been isolated which, when transfected into a benign rat mammary cell line induce the production of osteopontin and thereby endow those cells with the capability to metastasize in syngeneic rats. Using transient transfections of an osteopontin promoter-reporter construct, we have now identified the active moiety in the metastasis-inducing DNA as the binding site for the T cell factor (Tcf) family of transcription factors and located Tcf-4, beta-catenin and E-cadherin in the relevant DNA complex in vitro. The regulatory effects of the metastasis-inducing DNAs are therefore exerted, at least in part, by a CAAAG sequence which can sequester Tcf-4, thereby promoting transcription of the direct effector for metastasis in this system, osteopontin.
El-Tanani
M K
MK
Cancer and Polio Research Fund Laboratories, Molecular Medicine Group, School of Biological Sciences, University of Liverpool, Liverpool, L69 3BX, UK.
Barraclough
R
R
Wilkinson
M C
MC
Rudland
P S
PS
D000818:Animals; D001665:Binding Sites; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics*; D053495:Osteopontin; D011401:Promoter Regions, Genetic; D051381:Rats; D012795:Sialoglycoproteins / Q000235:genetics*; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004273:DNA, Neoplasm; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C553059:Tcf7l2 protein, rat; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D053495:Osteopontin