Down-regulation of beta catenin inhibits the growth of esophageal carcinoma cells.
BACKGROUND
Esophageal cancer remains a highly lethal malignancy, with therapeutic options of limited efficacy in the majority of patients. Understanding the molecular events involved in the pathogenesis of esophageal cancer offers insight into potential targets for treatment. Beta catenin and Wnt signaling abnormalities are involved in the development of both adenocarcinoma and squamous carcinoma of the esophagus. We hypothesized that down-regulation of beta catenin would inhibit the growth of human esophageal cancer.


METHODS
A human esophageal squamous cell carcinoma cell line (TE10) was treated with phosphorothioate antisense oligonucleotides to beta catenin. The cells were subsequently assayed for beta catenin mRNA and protein by real-time polymerase chain reaction and Western blot. Beta catenin transcriptional activity was determined by TOPFlash assay. Cell viability and growth was assessed by methyl-thiazol-diphenyl-tetrazolium assay and trypan blue exclusion. A colorimetric assay was employed to assess caspase 3 activity, and flow cytometry was done to determine percentage of cells in a given phase of the cell cycle.


RESULTS
Following antisense treatment, beta catenin mRNA and protein concentration were decreased. There was corresponding decrease in beta catenin-transcription factor-dependent transcription. Treatment with beta catenin antisense resulted in significantly decreased cell viability and proliferation. The mechanism appears to be increased induction of apoptosis.


CONCLUSIONS
These data suggest a potential role for the targeting of beta catenin in the treatment of esophageal cancer.
Veeramachaneni
Nirmal K
NK
Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Kubokura
Hirotoshi
H
Lin
Li
L
Pippin
James A
JA
Patterson
G Alexander
GA
Drebin
Jeffrey A
JA
Battafarano
Richard J
RJ
D000704:Analysis of Variance; D000912:Antibodies, Neoplasm / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D000912:Antibodies, Neoplasm; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin