Calpain is required for MMP-2 and u-PA expression in SV40 large T-antigen-immortalized cells.
The absence of both mu- and m-calpain activity, caused by disruption of the capn4 gene in mice, retarded migration, and disrupted the cytoskeleton, both in primary capn4(-/-) embryonic fibroblasts (mEF) and in capn4(-/-) mEF immortalized with SV40 large T-antigen (TAg). These results are thought to reflect the role of calpain in integrin signaling to the cytoskeleton. The integrins are also involved, together with matrix metalloproteinases (MMP) and plasminogen activators (PA), in cellular invasion. This study therefore aimed to establish whether links exist between the calpain, MMP, and PA systems, using both primary and TAg-immortalized capn4(+/+) and capn4(-/-) embryonic fibroblasts. Both Matrigel invasion, and expression of MMP-2 and u-PA activities, correlated with calpain expression in TAg-containing cells, but not in primary cells. MMP-2 mRNA synthesis also correlated with calpain expression in the presence of TAg, but u-PA mRNA synthesis was not so correlated. The results suggest that calpain acquires new regulatory roles in the presence of TAg. Calpain is also required for v-Src-mediated transformation. It appears that calpain may have previously unsuspected roles in oncogenic transformation.
Postovit
Lynne-Marie
LM
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ont., Canada K7L 3N6.
Dutt
Previn
P
Dourdin
Nathalie
N
Park
Minwoo
M
Greer
Peter A
PA
Graham
Charles H
CH
Elce
John S
JS
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013539:Simian virus 40 / Q000276:immunology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D002154:Calpain; D020778:Matrix Metalloproteinase 2