EurekaMag
+ Translate
+ Most Popular
Gaucher's disease;thirty-two years experience at Siriraj Hospital
A study of Macrobathra Meyrick from China (Lepidoptera, Cosmopterigidae)
First occurrence in ores of tetragonal chalcocite
Effects of trace element nutrition on sleep patterns in adult women
N.Z. range management guidelines. 2. Design of grazing management systems for tussock country
A case of lipoma of the esophagus
A revision of world Acanthosomatidae (Heteroptera: Pentatomidae): keys to and descriptions of subfamilies, tribes and genera, with designation of types
Life history of the coronate scyphozoan Linuche unguiculata (Swartz, 1788)
Perceptual restoration of obliterated sounds
Mutagenicity studies on two chromium(III) coordination compounds
The formation of the skeleton. I. Growth of a long bone. 1st appearance of a center of calcification
Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis
The joint commission: four key root causes loom large in sentinel event data
Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A
Behaviour of dairy cows within three hours after feed supply: I. Influence of housing type and time elapsing after feed supply
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS)
The diet composition and nutritional knowledge of patients with anorexia nervosa
Physoporella croatica Herak, 1958 of the Slovak karst Anisian (Slovakia, the West Carpathians Mts.)
Bright lights, big noise. How effective are vehicle warning systems?
Ein Plesiosaurier-Rest mit Magensteinen aus mittlerem Lias von Quedlinburg
Incidence of Chlamydia trachomatis in patients with sterility
Monster soup: the microscope and Victorian fantasy
Preliminary tests with residual sprays against poultry lice
Duration of the life of plants in phylogeny

Metastasis-inducing dna regulates the expression of the osteopontin gene by binding the transcription factor Tcf-4


Metastasis-inducing dna regulates the expression of the osteopontin gene by binding the transcription factor Tcf-4



Cancer Research 61(14): 5619-5629



ISSN/ISBN: 0008-5472

PMID: 11454716

Small 1,000-bp fragments of genomic DNA obtained from human malignant breast cancer cell lines when transfected into a benign rat mammary cell line enhance transcription of the osteopontin gene and thereby cause the cells to metastasize in syngeneic rats. To identify the molecular events underlying this process, transient cotransfections of an osteopontin promoter-reporter construct and fragments of one metastasis-inducing DNA (Met-DNA) have identified the active components in the Met-DNA as the binding sites for the T-cell factor (Tcf) family of transcription factors. Incubation of cell extracts with active DNA fragments containing the sequence CAAAG caused retardation of their mobilities on polyacrylamide gels, and Western blotting identified Tcf-4, beta-catenin, and E-cadherin in the relevant DNA complexes in vitro. Transfection of an expression vector for Tcf-4 inhibited the stimulated activity of the osteopontin promoter-reporter construct caused by transiently transfected active fragments of Met-DNA or permanently transfected Met-DNA. This stimulated activity of the osteopontin promoter-reporter construct is accompanied by an increase in endogenous osteopontin mRNA but not in fos or actin mRNAs in the transfected cells. Permanent transfection of the benign rat mammary cell line with a 20-bp fragment from the Met-DNA containing the Tcf recognition sequence CAAAG caused an enhanced permanent production of endogenous osteopontin protein in vitro and induced the cells to metastasize in syngeneic rats in vivo. The corresponding fragment without the CAAAG sequence was without either effect. Therefore, the regulatory effect of the C9-Met-DNA is exerted, at least in part, by a CAAAG sequence that can sequester the endogenous inhibitory Tcf-4 and thereby promote transcription of osteopontin, the direct effector of metastasis in this system.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 010978301

Download citation: RISBibTeXText

Related references

The functional -443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor. Molecular Carcinogenesis 48(1): 14-23, 2009

Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-kB and STAT3. The FASEB Journal 15(3): 2-4, 2001

Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3. Faseb Journal: Official Publication of the Federation of American Societies for Experimental Biology 15(3): 562-564, 2001

The tumor metastasis suppressor gene Drg-1 down-regulates the expression of activating transcription factor 3 in prostate cancer. Cancer Research 66(24): 11983-11990, 2006

Transcription factor AP-2 regulates human insulin-like growth factor binding protein-5 gene expression. Journal of Biological Chemistry 270(42): 24844-24851, 1995

Microsatellite instability regulates transcription factor binding and gene expression. Proceedings of the National Academy of Sciences of the United States of America 102(10): 3800-3804, 2005

A transcription factor cascade involving Fep1 and the CCAAT-binding factor Php4 regulates gene expression in response to iron deficiency in the fission yeast Schizosaccharomyces pombe. Eukaryotic Cell 5(11): 1866-1881, 2006

Transcription factor sterol regulatory element binding protein 2 regulates scavenger receptor Cla-1 gene expression. Arteriosclerosis Thrombosis and Vascular Biology 24(12): 2358-2364, 2004

Regulation of major histocompatibility (MHC) class II human leukocyte antigen-DR alpha gene expression in thyrocytes by single strand binding protein-1, a transcription factor that also regulates thyrotropin receptor and MHC class I gene expression. Endocrinology 139(5): 2300-2313, 1998

The CCAAT box binding transcription factor, nuclear factor-Y (NF-Y) regulates transcription of human aldo-keto reductase 1C1 (AKR1C1) gene. Gene 459(1-2): 11-23, 2010

CIZ, a transcription factor shuttling between nuclei and cell adhesion plaque, enhances Cbfa1 gene expression but counteracts against BMP signaling to resume osteopontin and to suppress collagen gene expression in osteoblast like cells. Journal of Bone and Mineral Research 16(Suppl 1): S174, 2001

Gene expression and transcription factor profiling reveal inhibition of transcription factor cAMP-response element-binding protein by gamma-herpesvirus replication and transcription activator. Journal of Biological Chemistry 285(33): 25139-25153, 2010

MMTV-associated transcription factor binding sites increase nm23-H1 metastasis suppressor gene expression in human breast carcinoma cell lines. Clinical and Experimental Metastasis 19(1): 35-42, 2002

A DNA variant within the MYO7A promoter regulates YY1 transcription factor binding and gene expression serving as a potential dominant DFNA11 auditory genetic modifier. Journal of Biological Chemistry 286(17): 15278-15286, 2011

C-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription. Journal of Experimental Medicine 194(8): 1021-1032, 2001