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

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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: