Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid.
All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E-cadherin/catenin complex was shown to be the most probable mechanism of the anti-invasive action. We did a series of experiments to determine whether the anti-invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF-I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action.
Vermeulen
S J
SJ
Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, University Hospital, Gent, Belgium.
Bruyneel
E A
EA
van Roy
F M
FM
Mareel
M M
MM
Bracke
M E
ME
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015820:Cadherins / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D014212:Tretinoin