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Modulation of alpha-actinin levels affects cell motility and confers tumorigenicity on 3T3 cells.

Abstract
alpha-Actinin is an abundant actin crosslinking protein, also localized at adherens type junctions. In adhesion plaques, alpha-actinin can link the actin filaments to integrin via vinculin and talin, or directly by binding to the cytoplasmic domain of beta 1-integrin. The expression of alpha-actinin is rapidly elevated in growth-activated quiescent cells, and is reduced in SV40-transformed 3T3 cells and various differentiating cell types (reviewed by Glück, U., Kwiatkowski, D. J. and Ben-Ze'ev, A. Proc. Nat. Acad. Sci. USA 90, 383-387, 1993). To study the effect of changes in alpha-actinin levels on cell behavior, alpha-actinin expression was elevated in 3T3 cells by transfection with a full-length human nonmuscle alpha-actinin cDNA. To suppress alpha-actinin levels, 3T3 cells were transfected with an antisense alpha-actinin cDNA construct. Cells overexpressing alpha-actinin by 40-60% displayed a significant reduction in cell motility, as demonstrated by their slower locomotion into an artificial wound, and by forming shorter phagokinetic tracks on colloidal gold-coated substrata. 3T3 cells in which the expression of alpha-actinin was reduced to 25-60% of control levels, after antisense alpha-actinin transfection, had an increased cell motility. Moreover, such alpha-actinin-deficient 3T3 cells formed tumors upon injection into nude mice. The results demonstrate that modulations in alpha-actinin expression can affect, in a major way, the motile and tumorigenic properties of cells, and support the view that decreased alpha-actinin expression could be a common regulatory pathway to malignant transformation of 3T3 cells.
AuthorsU Glück, A Ben-Ze'ev
JournalJournal of cell science (J Cell Sci) Vol. 107 ( Pt 7) Pg. 1773-82 (Jul 1994) ISSN: 0021-9533 [Print] ENGLAND
PMID7983147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • DNA, Complementary
  • Actinin
Topics
  • 3T3 Cells
  • Actinin (analysis, biosynthesis, isolation & purification)
  • Animals
  • Cell Movement
  • Cell Transformation, Neoplastic
  • DNA, Complementary (metabolism)
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental (pathology)
  • Restriction Mapping
  • Simian virus 40
  • Transfection

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