Adriamycin activates E-cadherin-mediated cell-cell adhesion in human breast cancer cells.
E-cadherin-mediated cell-cell adhesion plays a crucial role in intercellular communication, which is related to the regulation of cell proliferation, differentiation, and apoptosis. Our previous study showed that decreased expression of MUC1 can induce E-cadherin-mediated cell-cell adhesion in human breast cancer cell lines proliferating in suspension without aggregation. Using such a cell line (YMB-S), we observed the effects of an anticancer agent, adriamycin, on cell-cell adhesion and expression of E-cadherin-catenin complex and MUC1. The cells showed E-cadherin-mediated cell-cell adhesion after 48 h exposure to 0.4 micromol/l adriamycin. And in these cells, expression of E-cadherin and beta-catenin mRNA obviously began to increase, while expression of MUC1 mRNA decreased, as demonstrated by Northern blot analysis. Such change in mRNA levels were followed by increases in E-cadherin and beta-catenin protein levels and a decrease in MUC1 protein level. Though expression of alpha-catenin mRNA began to increase on day 2, its protein level did not change. In immunohistochemical analysis, beta-catenin protein in untreated cells showed diffuse cytoplasmic localization, whereas beta-catenin in treated cells was present in cytoplasm with a clear submembranous localization, indicating that increased beta-catenin mainly bound with E-cadherin, participating in cell-cell adhesion. These findings show for the first time that adriamycin can induce E-cadherin-mediated cell-cell adhesion by increasing expression of E-cadherin and beta-catenin and decreasing expression of MUC1 during breast cancer cell apoptosis induced by this drug.
Yang
S Z
SZ
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan.
Kohno
N
N
Kondo
K
K
Yokoyama
A
A
Hamada
H
H
Hiwada
K
K
Miyake
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018396:Mucin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
D000970:Antineoplastic Agents; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018396:Mucin-1; D012333:RNA, Messenger; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D004317:Doxorubicin