RRC ID |
6516
|
著者 |
Katabami K, Kato T, Sano R, Ogura M, Mizuno H, Itoh S, Tsuji T.
|
タイトル |
Characterization of the promoter for the alpha3 integrin gene in various tumor cell lines: roles of the Ets- and Sp-family of transcription factors.
|
ジャーナル |
J Cell Biochem
|
Abstract |
The alpha3beta1 integrin is an adhesion receptor for extracellular matrix proteins, including laminin isoforms, and plays crucial roles in the organization of epithelial and endothelial tissues. The aberrant expression of this adhesion molecule on tumor cells is associated with their invasive and metastatic potentials. In the present study, we analyzed the elements essential for alpha3 integrin gene expression in various tumor cell lines with different tissue origins by luciferase assay. An approximately 0.3 kb fragment of the 5'-flanking region of the mouse alpha3 integrin gene (-260/+84, relative to the major transcription start site) showed strong promoter activity in all six examined tumor cell lines. However, we found that these cell lines could be divided into two groups according to the level of dependency on the putative Ets-transcription factor binding motif located at -133. This motif was previously shown to be crucial for alpha3 integrin expression in MKN1 gastric carcinoma cells. The gene expression in one group of cell lines was upregulated mainly by the Ets motif, whereas that in the other group was less dependent on the Ets motif. We then postulated that additional regulatory elements were responsible for the expression of alpha3 integrin, and found that a GC-rich motif at -69 was another important element. An electrophoretic mobility shift assay using specific antibodies and a Western blot analysis of nuclear proteins revealed that the Sp3-transcription factor bound to this GC-rich motif. These results suggest that the Sp3 and Ets transcription factors cooperatively regulate alpha3 integrin gene expression and that the contribution of each element depends on the type of tumor cells.
|
巻・号 |
97(3)
|
ページ |
530-43
|
公開日 |
2006-2-15
|
DOI |
10.1002/jcb.20663
|
PMID |
16211576
|
MeSH |
Animals
Base Sequence
Binding Sites
Blotting, Western
Cell Line, Tumor
Electrophoretic Mobility Shift Assay
GC Rich Sequence
Gene Expression Regulation, Neoplastic
Humans
Integrin alpha3beta1 / genetics*
Luciferases / metabolism
Mice
Molecular Sequence Data
Neoplasms / metabolism
Promoter Regions, Genetic*
Proto-Oncogene Proteins c-ets / physiology*
Sequence Deletion
Sequence Homology, Nucleic Acid
Sp3 Transcription Factor / physiology*
Transcription Initiation Site
Transcription, Genetic
|
IF |
4.237
|
引用数 |
5
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MKN1(RCB1003) |