Exogenous Expression of {beta}-Catenin Regulates Contact Inhibition, Anchorage-independent Growth, Anoikis, and Radiation-induced Cell Cycle Arrest

doi:10.1083/jcb.146.4.855

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J. Cell Biol., Volume 146, Number 4, August 23, 1999 855-868
Copyright © 1999 by The Rockefeller University Press.

Exogenous Expression of ß-Catenin Regulates Contact Inhibition, Anchorage-independent Growth, Anoikis, and Radiation-induced Cell Cycle Arrest

Keith Orford^a, Caroline C. Orford^a, and Stephen W. Byers^a
^a The Lombardi Cancer Center and the Department of Cell Biology, Georgetown University School of Medicine, Washington, District of Columbia 20007

Correspondence to: Stephen W. Byers, E415 The Research Building, GUMC, 3970 Reservoir Road N.W., Washington, DC 20007. Tel:(202) 687-1813 Fax:(202) 687-7505 E-mail:byerss{at}gunet.georgetown.edu.

ß-Catenin is an important regulator of cell–celladhesion and embryonic development that associates with andregulates the function of the LEF/TCF family of transcriptionfactors. Mutations of ß-catenin and the tumor suppressorgene, adenomatous polyposis coli, occur in human cancers, butit is not known if, and by what mechanism, increased ß-catenincauses cellular transformation. This study demonstrates thatmodest overexpression of ß-catenin in a normal epithelialcell results in cellular transformation. These cells form coloniesin soft agar, survive in suspension, and continue to proliferateat high cell density and following ${gamma}$ -irradiation. Endogenouscytoplasmic ß-catenin levels and signaling activity werealso found to oscillate during the cell cycle. Taken together,these data demonstrate that ß-catenin functions as anoncogene by promoting the G₁ to S phase transition and protectingcells from suspension-induced apoptosis (anoikis).

Key Words: ß-catenin, oncogene, cell cycle, anoikis, apoptosis

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