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1 April 2001 E-Cadherin-Mediated Cell Contact Prevents Apoptosis of Spontaneously Immortalized Granulosa Cells by Regulating Akt Kinase Activity
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The present studies were designed to determine the role that homophilic E-cadherin binding plays in preventing apoptosis of spontaneously immortalized granulosa cells (SIGCs). Although the levels of E-cadherin were similar to serum control levels, the amount of E-cadherin at the plasma membrane was dramatically reduced by 5 h after serum withdrawal. To determine whether disrupting homophilic E-cadherin binding leads to apoptosis, SIGCs were cultured in serum in the presence of either EGTA or an E-cadherin antibody. Treatment with either EGTA, which disrupts all calcium-dependent contacts, or E-cadherin antibody, induced apoptosis. Exposure to EGTA reduced MEK and Akt kinase activity, whereas E-cadherin antibody only attenuated Akt kinase activity. Because Akt kinase controls caspase-3 activity, an important activator of apoptosis, caspase-3 activity was monitored. Caspase-3 activity increased after serum depletion, or EGTA or E-cadherin antibody treatment. Time-series analysis of caspase-3 activity within single cells revealed that during apoptosis cell contact was disrupted then caspase-3 activity was detected. Finally, the caspase inhibitor, Z-VAD-FMK, blocked apoptosis. These data taken together are consistent with the concept that E-cadherin-mediated cell contact, either directly or indirectly, promotes Akt kinase activity, which in turn, inhibits caspase-3 activation and thereby maintains SIGC viability.

J. J. Peluso, A. Pappalardo, and G. Fernandez "E-Cadherin-Mediated Cell Contact Prevents Apoptosis of Spontaneously Immortalized Granulosa Cells by Regulating Akt Kinase Activity," Biology of Reproduction 64(4), 1183-1190, (1 April 2001).
Received: 25 August 2000; Accepted: 1 November 2000; Published: 1 April 2001

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