| RRC ID |
42316
|
| 著者 |
Naishiro Y, Yamada T, Idogawa M, Honda K, Takada M, Kondo T, Imai K, Hirohashi S.
|
| タイトル |
Morphological and transcriptional responses of untransformed intestinal epithelial cells to an oncogenic beta-catenin protein.
|
| ジャーナル |
Oncogene
|
| Abstract |
Aberrant transactivation of a certain set of target genes by the beta-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor complexes has been implicated in the process of intestinal epithelial cells entering early colorectal carcinogenesis. A rat intestinal epithelial cell line IEC6 became elongated, extended protrusions at cell periphery, and increased stress fibers and focal contacts upon the induction of beta-catenin protein stabilized by deletion of the N-terminal glycogen synthase kinase-3beta (GSKbeta) phosphorylation sites (beta-catenin DeltaN89). We used the GeneChiptrade mark oligonucleotide microarray system to examine approximately 24 000 genes and identified 13 genes whose expression was altered during the course of this morphological transformation. Those genes included known negative regulators of the Wnt signaling pathway, Sfrp4 and Axin2; extracellular matrix and related molecule, Hxb and Crtl1; cell adhesion and cytoskeletal proteins, Podxl, Igaf4, and Itab6; and molecules involved in the insulin and insulin-like growth factor (IGF) signaling pathways, Enpp1, Igfbp2, and Sgk. We report the finding that insulin-like growth factor-binding protein-2 (IGFBP2) is a direct target gene of the beta-catenin and TCF/LEF complexes. The IGFBP2 protein interacts with integrins. Disruption of the multigene network system regulating cell adhesion and cytoskeleton may be crucial in the initiation of colorectal carcinogenesis.
|
| 巻・号 |
24(19)
|
| ページ |
3141-53
|
| 公開日 |
2005-4-28
|
| DOI |
10.1038/sj.onc.1208517
|
| PII |
1208517
|
| PMID |
15735679
|
| MeSH |
Adenoma / metabolism
Animals
Cell Adhesion
Cell Line
Cell Line, Transformed
Cell Line, Tumor
Cell Transformation, Neoplastic*
Cells, Cultured
Chromatin Immunoprecipitation
Colon / metabolism
Colorectal Neoplasms / metabolism
Cytoskeletal Proteins / metabolism*
DNA-Binding Proteins / metabolism
Epithelial Cells / metabolism*
Extracellular Matrix / metabolism
Gene Expression Regulation, Neoplastic*
Genes, Reporter
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
HeLa Cells
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins / metabolism
Intestinal Mucosa / metabolism*
Intestine, Small / metabolism
Luciferases / metabolism
Lymphoid Enhancer-Binding Factor 1
Male
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Oligonucleotide Array Sequence Analysis
Protein Structure, Tertiary
Rats
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
Trans-Activators / metabolism*
Transcription Factors / metabolism
Transcription, Genetic*
Wnt Proteins
beta Catenin
|
| IF |
7.971
|
| 引用数 |
35
|
|
WOS 分野
|
GENETICS & HEREDITY
ONCOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
293(RCB1637) |
