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Molecular and Cellular Biology, January 2003, p. 566-578, Vol. 23, No. 2
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.2.566-578.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

T-Cadherin-Mediated Cell Growth Regulation Involves G2 Phase Arrest and Requires p21CIP1/WAF1 Expression

Zhi-yong Huang, YanLi Wu, Nicolé Hedrick, and David H. Gutmann*

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri

Received 29 July 2002/ Returned for modification 7 October 2002/ Accepted 17 October 2002

Members of the cadherin family have been implicated as growth regulators in multiple tumor types. Based on recent studies from our laboratory implicating T-cadherin expression in mouse brain tumorigenesis, we examined the role of T-cadherin in astrocytoma growth regulation. In this report, we show that T-cadherin expression increased during primary astrocyte physiologic growth arrest in response to contact inhibition and serum starvation in vitro, suggesting a function for T-cadherin in astrocyte growth regulation. We further demonstrate that transient and stable reexpression of T-cadherin in deficient C6 glioma cell lines results in growth suppression. In addition, T-cadherin-expressing C6 cell lines demonstrated increased homophilic cell aggregation, increased cell attachment to fibronectin, and decreased cell motility. Cell cycle flow cytometry demonstrated that T-cadherin reexpression resulted in G2 phase arrest, which was confirmed by mitotic index analysis. This growth arrest was p53 independent, as T-cadherin could still mediate growth suppression in p53-/- mouse embryonic fibroblasts. T-cadherin-expressing C6 cell lines exhibited increased p21CIP1/WAF1, but not p27Kip1, expression. Lastly, T-cadherin-mediated growth arrest was dependent on p21CIP1/WAF1 expression and was eliminated in p21CIP1/WAF1-deficient fibroblasts. Collectively, these observations suggest a novel mechanism of growth regulation for T-cadherin involving p21CIP1/WAF1 expression and G2 arrest.

* Corresponding author. Mailing address: Department of Neurology, Washington University School of Medicine, Box 8111; 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-7379. Fax: (314) 362-2388. E-mail: gutmannd{at}neuro.wustl.edu.

Molecular and Cellular Biology, January 2003, p. 566-578, Vol. 23, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.2.566-578.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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