Transcriptomics

Dataset Information

3

FOXO3a and beta-catenin transcriptional profile in human colon cancer cell line DLD1


ABSTRACT: We established a model system in human DLD1 colon cancer cells to study the transcriptional crosstalk between FOXO3A and beta-Catenin. Thereby, translocation to the nucleus of a AKT-insensitive mutant (T32A, S253A, S315A) of human FOXO3A fused to the ligand binding domain of human estrogen receptor can be induced by exposure to 4-hydroxy-tamoxifen. Furthermore, expression of a stable mutant (S33Y) of human beta-catenin is doxycycline inducible. Addition of those drugs separately or in combination allows identification of common or excusive target gene sets.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

DISEASE(S): Colorectal Adenocarcinoma

SUBMITTER: Stephan P Tenbaum  

PROVIDER: E-MEXP-3262 | ArrayExpress | 2012-05-01

REPOSITORIES: ArrayExpress

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Publications


The Wnt–β-catenin and PI3K-AKT-FOXO3a pathways have a central role in cancer. AKT phosporylates FOXO3a, relocating it from the cell nucleus to the cytoplasm, an effect that is reversed by PI3K and AKT inhibitors. Simultaneous hyperactivation of the Wnt–β-catenin pathway and inhibition of PI3K-AKT signaling promote nuclear accumulation of β-catenin and FOXO3a, respectively, promoting cell scattering and metastasis by regulating a defined set of target genes. Indeed, the anti-tumoral AKT inhibitor  ...[more]

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