Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines.
Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.
Kondo
K
K
Second Department of Internal Medicine, Ehime University School of Medicine, Japan.
Kohno
N
N
Yokoyama
A
A
Hiwada
K
K
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D015820:Cadherins / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
D002087:Butyrates; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018396:Mucin-1; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D020148:Butyric Acid; D014443:Tyrosine; D007930:Leucine; C012211:ubenimex