Repression of Platelet-Derived Growth Factor β-Receptor Expression by Mitogenic Growth Factors and Transforming Oncogenes in Murine 3T3 Fibroblasts

Vaziri, Cyrus; Faller, Douglas V.

doi:10.1128/mcb.15.3.1244

Cited by 50 publications

(55 citation statements)

References 58 publications

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“…For example we showed that PDGF␤ receptor (PDGF␤R) expression is elevated in quiescent cells and is transcriptionally down-regulated concomitantly with cell cycle re-entry (39). It appears that PDGF␤R induction during quiescence "primes" growth-arrested cells for stimulation by PDGF, and that PDGF␤R down-regulation during cell cycle entry represents a desensitization mechanism to prevent excessive or aberrant PDGFR signaling.…”

Section: Discussionmentioning

confidence: 99%

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Rocnik

Liu

Sato

et al. 2006

Journal of Biological Chemistry

106

109

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SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent with a growth-stimulatory role for SMOC-2, its overexpression stimulated DNA synthesis in a dosedependent manner. Overexpressed SMOC-2 also synergized with vascular endothelial growth factor or with basic fibroblast growth factor to stimulate DNA synthesis. Ectopically expressed SMOC-2 stimulated formation of network-like structures as determined by in vitro matrigel angiogenesis assays. Fetal calf serum enhanced the stimulatory effect of overexpressed SMOC-2 in this assay. Conversely, small interference RNA directed toward SMOC-2 inhibited network formation and proliferation. The angiogenic activity of SMOC-2 was also examined in experimental mice by subdermal implantation of Matrigel plugs containing SMOC-2 adenovirus. SMOC-2 adenovirus induced a 3-fold increase in the number of cells invading Matrigel plugs when compared with a control adenoviral vector. Basic fibroblast growth factor and SMOC-2 elicited a synergistic effect on cell invasion. Taken together, our results demonstrate that SMOC-2 is a novel angiogenic factor that potentiates angiogenic effects of growth factors.

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Section: Discussionmentioning

confidence: 99%

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Rocnik

Liu

Sato

et al. 2006

Journal of Biological Chemistry

106

109

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“…These ®ndings provide functional evidence that the hybrid polar compounds SAHA and HMBA trigger leukemic cell death through fundamentally di erent cell cycle checkpoint-related mechanisms. In this regard, the histone deacetylase inhibitor sodium butyrate has recently been shown to induce G 1 arrest and pRb dephosphorylation in 3T3 cells lacking p21 CIP1 (Vaziri et al, 1998). Whether histone deacetylase inhibitors speci®cally exert their antiproliferative e ects through a p21 CIP1 -independent mechanism remains an unresolved issue.…”

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

et al. 1999

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Determinants of di erentiation and apoptosis in myelomonocytic leukemia cells (U937) exposed to the novel hybrid polar compound SAHA (suberoylanilide hydroxamic acid) have been examined. In contrast to hexamethylenbisacetamide (HMBA), SAHA-related maturation was limited and accompanied by marked cytoxicity. SAHA-mediated apoptosis occurred within the G 0 G 1 and S phase populations, and was associated with decreased mitochondrial membrane potential, caspase-3 activation, PARP degradation, hypophosphorylation/cleavage of pRB, and down-regulation of c-Myc, c-Myb, and B-Myb. Enforced expression of Bcl-2 or Bclx L inhibited SAHA-induced apoptosis, but only modestly potentiated di erentiation. While SAHA induced the cyclin-dependent kinase inhibitor p21 CIP1 , antisense ablation of this CDKI increased, rather than decreased, SAHA-related lethality. In contrast, conditional expression of wild-type p53 failed to modify SAHA actions, but markedly potentiated HMBA-induced apoptosis. Finally, SAHA modestly increased expression/activation of the stress-activated protein kinase (SAPK/JNK); moreover, SAHA-related lethality was partially attenuated by a dominant-negative c-Jun mutant protein (TAM67). SAHA did not stimulate mitogen-activated protein kinase (MAPK), nor was lethality diminished by the speci®c MEK/MAPK inhibitor PD98059. These ®ndings indicate that SAHA potently induces apoptosis in human leukemia cells via a pathway that is p53-independent but at least partially regulated by Bcl-2/Bcl-x L , p21 CIP1 , and the c-Jun/AP-1 signaling cascade.

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“…The expression of the b-chain of the PDGF receptor in mouse ®broblasts was shown to be repressed by the vras or v-src oncogenes (Vaziri and Faller, 1995). The reduced number of cell surface PDGF receptors present in transformed ®broblasts may desensitize the cells to subsequent stimulation by PDGF.…”

Section: Discussionmentioning

confidence: 99%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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Repression of Platelet-Derived Growth Factor β-Receptor Expression by Mitogenic Growth Factors and Transforming Oncogenes in Murine 3T3 Fibroblasts

Cited by 50 publications

References 58 publications

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53

Transformation by ras modifies AP1 composition and activity

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