Linked Life Data

15735752

Source:http://linkedlifedata.com/resource/pubmed/id/15735752

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2005-5-13
pubmed:abstractText
Recently, E2F function has expanded to include the regulation of differentiation in human epidermal keratinocytes (HEKs). We extend these findings to report that in HEKs, Sp1 is a differentiation-specific activator and a downstream target of E2F-mediated suppression of the differentiation-specific marker, transglutaminase type 1 (TG-1). Deletion of elements between -0.084 to -0.034 kb of the TG-1 promoter disabled E2F1-induced suppression of promoter activity. Electrophoretic mobility shift assays (EMSAs) demonstrated that Sp1 and Sp3 bound this region. Protein expression analysis suggested that squamous differentiation was accompanied by increased Sp1/Sp3 ratio. Cotransfection of proliferating HEKs or the squamous cell carcinoma (SCC) cell line, KJD-1/SV40, with an E2F inhibitor (E2Fd/n) and Sp1 expression plasmid was sufficient to activate the TG-1 promoter. The suppression of Sp1 activity by E2F in differentiated cells appeared to be indirect since we found no evidence of an Sp1/E2F coassociation on the TG-1 promoter fragment. Moreover, E2F inhibition in the presence of a differentiation stimulus induced Sp1 protein. These data demonstrate that (i) Sp1 can act as a differentiation stimulus, (ii) E2F-mediated suppression of differentiation-specific markers is indirect via Sp1 inhibition and (iii) a combination of E2F inhibition and Sp1 activation could form the basis of a differentiation therapy for SCCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3525-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15735752-Carcinoma, Squamous Cell, pubmed-meshheading:15735752-Cell Cycle Proteins, pubmed-meshheading:15735752-Cell Differentiation, pubmed-meshheading:15735752-DNA-Binding Proteins, pubmed-meshheading:15735752-Down-Regulation, pubmed-meshheading:15735752-E2F Transcription Factors, pubmed-meshheading:15735752-E2F1 Transcription Factor, pubmed-meshheading:15735752-Electrophoretic Mobility Shift Assay, pubmed-meshheading:15735752-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15735752-Humans, pubmed-meshheading:15735752-Keratinocytes, pubmed-meshheading:15735752-Sp1 Transcription Factor, pubmed-meshheading:15735752-Transcription Factors, pubmed-meshheading:15735752-Transfection, pubmed-meshheading:15735752-Transglutaminases, pubmed-meshheading:15735752-Tumor Cells, Cultured, pubmed-meshheading:15735752-Tumor Markers, Biological, pubmed-meshheading:15735752-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
E2F suppression and Sp1 overexpression are sufficient to induce the differentiation-specific marker, transglutaminase type 1, in a squamous cell carcinoma cell line.
pubmed:affiliation
Epithelial Pathobiology Group, Cancer Biology Programme, Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't