T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires p21(CIP1/WAF1) expression.

Abstract

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 p21(CIP1/WAF1), but not p27(Kip1), expression. Lastly, T-cadherin-mediated growth arrest was dependent on p21(CIP1/WAF1) expression and was eliminated in p21(CIP1/WAF1)-deficient fibroblasts. Collectively, these observations suggest a novel mechanism of growth regulation for T-cadherin involving p21(CIP1/WAF1) expression and G2 arrest.

• Authors: Zhi-yong Huang, YanLi Wu, Nicolé Hedrick, David H Gutmann
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 23 Issue 2 Pg. 566-78 (Jan 2003) ISSN: 0270-7306 [Print] United States
• PMID: 12509455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cadherins
• Cdkn1a protein, mouse
• Cdkn1a protein, rat
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• H-cadherin
• DNA

Topics

• Aneuploidy
• Animals
• Blotting, Western
• Brain Neoplasms (metabolism)
• Cadherins (genetics, metabolism, physiology)
• Cell Adhesion
• Cell Division
• Cell Movement
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (biosynthesis, physiology)
• DNA (metabolism)
• Fibroblasts (metabolism)
• Flow Cytometry
• G2 Phase
• Mice
• Mitosis
• Protein Biosynthesis
• Rats
• Time Factors
• Transcription, Genetic
• Transfection
• Tumor Cells, Cultured