Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin.
The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/).
Germann
Anja
A
Division of Molecular Pathology, Department of Pathology, University Hospital of Heidelberg, Heidelberg, Germany.
Dihlmann
Susanne
S
Hergenhahn
Manfred
M
Doeberitz
Magnus von Knebel
Mv
Koesters
Robert
R
D001241:Aspirin / Q000494:pharmacology*; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D002087:Butyrates; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin; D001241:Aspirin