Decreased E-cadherin augments beta-catenin nuclear localization: studies in breast cancer cell lines.
We showed that the YMB-1-derived breast cancer cell line YMB-S, which proliferates in suspension without aggregation, exhibits complete loss of cell-cell adhesion despite the presence of E-cadherin-catenin complex and expression of free beta-catenin in the cytoplasm. Here, we describe beta-catenin gene regulation, interaction with E-cadherin, immunocytochemical localization, and their relation to growth rate in the YMB-1-derived cell line YMB-A, which forms tight junctions and displays anchorage-dependent growth. YMB-A cells proliferated more slowly than YMB-S cells. E-cadherin and APC gene product expression in YMB-A cells was significantly higher than that in YMB-S cells, whereas expression of beta-catenin, MUC1, and c-myc was lower in YMB-A cells than in YMB-S cells. According to immunocytochemical analysis, beta-catenin in YMB-A cells displayed membranous or submembranous localization, indicating that beta-catenin is mostly tethered to E-cadherin. Inhibition of E-cadherin expression in YMB-A cells by an antisense oligonucleotide did not change expression of whole cell beta-catenin protein, but increased nuclear beta-catenin protein level, c-myc expression, and cell growth rate. These results suggest that decreased expression of E-cadherin and APC and increased amount of beta-catenin in YMB-S cells lead to accumulation of beta-catenin in the nucleus, activate beta-catenin-LEF/TCF signaling pathway, and trigger c-myc proto-oncogene expression. c-Myc overexpression in breast cancer may be related to activated Wnt independent beta-catenin-LEF/TCF signaling.
Yang
S Z
SZ
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan.
Kohno
N
N
Yokoyama
A
A
Kondo
K
K
Hamada
H
H
Hiwada
K
K
D015139:Blotting, Southern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D017491:Genes, APC / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D000090063:Proto-Oncogene Mas; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C000715470:MAS1 protein, human; D018396:Mucin-1; D000090063:Proto-Oncogene Mas; D015534:Trans-Activators; D051176:beta Catenin