Transient induction of vinculin gene expression in 3T3 fibroblasts stimulated by serum-growth factors.

Ben-Ze’ev, Avri; Reiss, Rebecca A.; Bendori, R; Gorodecki, Barbara

doi:10.1091/mbc.1.9.621

Cited by 45 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The suppression of tumorigenicity was observed with the vinculin-transfected cells in both syngeneic and nude mice which have a compromised immune system, suggesting that immunological reactions are apparently not the cause for the effect observed. This conclusion is also supported by the fact that vinculin is a highly conserved protein (Price et al, 1989;Weller et al, 1990;Ben-Ze'ev et al, 1990), and thus a poor immunogen, and being an intraceltular protein, it is not exposed to the immune system. Moreover, overexpression of another cellular protein, such as a mutant murine p53 cDNA which lacks the nuclear localization signals (Shaulsky et al, 1991), had no effect on the tumorigenicity of SVT2 cells (data not shown).…”

Section: Discussionmentioning

confidence: 83%

Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Rodrı́guez-Fernández

Geiger

Salomon

et al. 1992

The Journal of Cell Biology

Self Cite

211

View full text Add to dashboard Cite

Abstract. Transfection of chicken vinculin cDNA into two tumor cell lines expressing diminished levels of the endogenous protein, brought about a drastic suppression of their tumorigenic ability. The SV-40-transformed Balb/e 3T3 line (SV'F2) contains four times less vinculin than the parental 3T3 cells, and the rat adenocarcinoma BSp73ASML has no detectable vinculin. Restoration of vinculin in these cells, up to the levels found in 3T3 cells, resulted in an apparent increase in substrate adhesiveness, a decrease in the ability to grow in soft agar, and suppression of their eapacity to develop tumors after injection into syngeneic hosts or nude mice. These results suggest that vinculin, a cytoplasmic component of cell-matrix and cell-cell adhesions, may have a major suppressive effect on the transformed phenotype.

show abstract

Section: Discussionmentioning

confidence: 83%

Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Rodrı́guez-Fernández

Geiger

Salomon

et al. 1992

The Journal of Cell Biology

Self Cite

211

View full text Add to dashboard Cite

show abstract

“…This has been shown, for example, in neural cells where EGF and FGF can di erentially upregulate the expression of several proteins (Loret et al, 1989). Similarly, in ®broblasts FGF, but not EGF, upregulates the vinculin gene (Ben-Ze'ev et al, 1990).…”

Section: Introductionmentioning

confidence: 87%

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner

1998

View full text Add to dashboard Cite

The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in ®broblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In ®broblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in ®broblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factorstimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in ®broblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in ®broblasts. Thirdly, EGF, which did not activate FiRE in ®broblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in ®broblasts. These data suggest mechanisms by which members of the EGF-and FGF-families can di erentially stimulate transcription through AP-1 regulated elements in a cell type-speci®c manner.

show abstract

“…Total RNA was extracted by the guanidinium thiocyanate method (30). Northern blots containing total RNA (20 pug per lane) were stained with methylene blue to determine the position of 18S and 28S rRNA markers and then hybridized (sequentially) with a-actinin and glyceraldehyde-3-phosphate dehydrogenase cDNA probes, which were labeled with P2P]dCTP by the random-priming technique (31), as described (32 (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Glück

Kwiatkowski

Ben-Ze’ev

1993

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

140

View full text Add to dashboard Cite

Human cytoskeletal a-actinin cDNA was transfected into highly malignant simian virus 40-transformed BALB/c 3T3 (SVT2) cells that express 6-fold lower levels of a-actinin than nontransformed BALB/c 3T3 cells. SVT2 clones expressing various levels of a-actinin were isolated and their structure and tumorigenic properties were determined. Transfected SVT2 clones expressing a-actinin at levels found in nontumorigenic 3T3 cells displayed a flatter phenotype, a decreased ability to grow in suspension culture in soft agar, and a marked reduction in their ability to form tumors in syngeneic BALB/c mice and in athymic nude mice. Clones overexpressing a-actinin at the highest level (about 2-fold higher than 3T3 cells) were completely suppressed in their ability to form tumors in syngeneic BALB/c mice. The results suggest that a-actinin, an actin-crosslinking protein that is also localized in cell junctions, may have an effective suppressive ability on the transformed phenotype.Malignant transformation of cells is characterized by alterations in cell growth, adhesion, motility, and cell shape (1). Among the more conspicuous morphological alterations in transformed cells are a round phenotype and a decrease in the number of microfilament bundles (2, 3). The disorganization of the actin filaments in transformed cells is often associated with a reduced expression of microfilament proteins such as tropomyosin (4), gelsolin (5), and vinculin (6). These changes in microfilaments correlate with the ability of cells to grow in suspension in semisolid medium (7).Previous studies have demonstrated a reversion in the transformed phenotype of cancer cells in the presence of a variety of agents and a return to the original malignant behavior upon their removal (8). This "reverse transformation" includes a reversible modulation in cell shape and the organization of the cytoskeleton (9). However, the relationships between the changes in growth properties and the altered cell structure of transformed cells are still unknown (10). Do the characteristic changes in cell morphology of transformed cells result from alterations in the rate of growth or are changes in cell adhesion and cytostructure responsible for disruption of the adhesion-dependent growth control? In this study we addressed this question directly by modulating the expression ofa single actin-associated protein a-actinin in a tumorigenic cell line and determined the consequences of altered a-actinin expression on the phenotype of the cells. a-Actinin is an abundant cytoplasmic actin-binding protein (11) that crosslinks actin filaments in vitro and is found in both muscle and nonmuscle cells (12,13). In striated muscle cells, a-actinin is localized in Z-disks; in smooth muscle cells, it is in dense plaques; and in nonmuscle cells, a-actinin is found along microfilaments (14) and in adherens junctions (AJs), at sites where actin filaments attach to the membrane (15)(16)(17). The role of a-actinin in mediating actin attachment to the membrane is not completely understood. ...

show abstract

Transient induction of vinculin gene expression in 3T3 fibroblasts stimulated by serum-growth factors.

Cited by 45 publications

References 53 publications

Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Contact Info

Product

Resources

About