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Vol. 16, Issue 3, 1330-1340, March 2005

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The Roles of Versican V1 and V2 Isoforms in Cell Proliferation and Apoptosis

Wang Sheng ^* , Guizhi Wang ^* , Yelina Wang ^* , Jiyong Liang ^* , Jianping Wen ^*, Peng-Sheng Zheng ^* , Yaojiong Wu ^* , Vivian Lee ^* , Joyce Slingerland ^* , Dan Dumont ^* , and Burton B. Yang ^* 

^* Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1A1, Canada; and Department of Medical Biophysics, University of Toronto, Ontario M5S 1A1, Canada

Submitted April 8, 2004; Revised December 10, 2004; Accepted December 12, 2004
Monitoring Editor: Richard Hynes

Versican is a large chondroitin sulfate proteoglycan belonging to the lectican family. Alternative splicing of versican generates at least four isoforms named V0, V1, V2, and V3. We have shown that the versican V1 isoform not only enhanced cell proliferation, but also modulated cell cycle progression and protected the cells from apoptosis. Futhermore, the V1 isoform was able to not only activate proto-oncogene EGFR expression and modulate its downstream signaling pathway, but also induce p27 degradation and enhance CDK2 kinase activity. As well, the V1 isoform down-regulated the expression of the proapoptotic protein Bad. By contrast, the V2 isoform exhibited opposite biological activities by inhibiting cell proliferation and down-regulated the expression of EGFR and cyclin A. Furthermore, V2 did not contribute apoptotic resistance to the cells. In light of these results, we are reporting opposite functions for the two versican isoforms whose expression is differentially regulated. Our studies suggest that the roles of these two isoforms are associated with the subdomains CS and CS, respectively. These results were confirmed by silencing the expression of versican V1 with small interfering RNA (siRNA), which abolished V1-enhanced cell proliferation and V1-induced reduction of apoptosis.

Abbreviations used: EGF, epidermal growth factor; EGFR, EGF receptor; G3, selectin-like domain; CRD, carbohydrate recognition domain; CBP, complement binding protein; FBS, fetal bovine serum; HBSS, Hanks' balanced salt solution; siRNA, small interfering RNA.

Address correspondence to: Burton B. Yang (Burton.Yang{at}sw.ca).

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