Lanthanum Induces Extracellular Signal-regulated Kinase Phosphorylation through Different Mechanisms in HeLa Cells and NIH 3T3 Cells

BioMetals ◽  
2006 ◽  
Vol 19 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Jian Hu ◽  
Siwang Yu ◽  
Xiaoda Yang ◽  
Kui Wang ◽  
Zhongming Qian
Keyword(s):  
Hela Cells ◽  
3T3 Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Kinase Phosphorylation ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling Pathway

2001 ◽  
Vol 21 (9) ◽  
pp. 3192-3205 ◽  
Author(s):  
Douglas Woods ◽  
Holly Cherwinski ◽  
Eleni Venetsanakos ◽  
Arun Bhat ◽  
Stephan Gysin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Integrin Expression ◽  
3T3 Cells ◽  
Extracellular Signal ◽  
Integrin Gene ◽  
Β3 Integrin ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf–MEK–extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of α6- and β3-integrin. Consistent with this, conditional activation of the Raf-MEK-ERK pathway in NIH 3T3 cells led to a 5 to 20-fold induction of cell surface α6- and β3-integrin expression. Induced β3-integrin was expressed on the cell surface as a heterodimer with αv-integrin; however, the overall level of αv-integrin expression was not altered by Ras or Raf. Raf-induced β3-integrin was observed in primary and established mouse fibroblast lines and in mouse and human endothelial cells. Consistent with previous reports of the ability of the Raf-MEK-ERK signaling pathway to induce β3-integrin gene transcription in human K-562 erythroleukemia cells, Raf activation in NIH 3T3 cells led to elevated β3-integrin mRNA. However, unlike immediate-early Raf targets such as heparin binding epidermal growth factor and Mdm2, β3-integrin mRNA was induced by Raf in a manner that was cycloheximide sensitive. Surprisingly, activation of the Raf-MEK-ERK signaling pathway by growth factors and mitogens had little or no effect on β3-integrin expression, suggesting that the expression of this gene requires sustained activation of this signaling pathway. In addition, despite the robust induction of cell surface αvβ3-integrin expression by Raf in NIH 3T3 cells, such cells display decreased spreading and adhesion, with a loss of focal adhesions and actin stress fibers. These data suggest that oncogene-induced alterations in integrin gene expression may participate in the changes in cell adhesion and migration that accompany the process of oncogenic transformation.

scholarly journals Cyclic AMP Blocks Cell Growth through Raf-1-Dependent and Raf-1-Independent Mechanisms

2002 ◽  
Vol 22 (11) ◽  
pp. 3717-3728 ◽  
Author(s):  
Nicolas Dumaz ◽  
Yvonne Light ◽  
Richard Marais
Keyword(s):  
Protein Kinase ◽  
Cell Growth ◽  
Cyclic Amp ◽  
3T3 Cells ◽  
Extracellular Signal ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT It is widely accepted that cyclic AMP (cAMP) can block cell growth by phosphorylating Raf-1 on serine 43 and inhibiting signaling to extracellular signal-regulated protein kinase. We show that the suppression of Raf-1 by cAMP is considerably more complex than previously reported. When cellular cAMP is elevated, Raf-1 is phosphorylated on three residues (S43, S233, and S259), which work independently to block Raf-1. Both Ras-dependent and Ras-independent processes are disrupted. However, when cAMP-insensitive versions of Raf-1 are expressed in NIH 3T3 cells, their growth is still strongly suppressed when cAMP is elevated. Thus, although Raf-1 appears to be an important cAMP target, other pathways are also targeted by cAMP, providing alternative mechanisms that lead to suppression of cell growth.

scholarly journals Cell-specific regulation of oncogene-responsive sequences of the c-fos promoter

1991 ◽  
Vol 11 (10) ◽  
pp. 5381-5387
Author(s):  
A Gutman ◽  
C Wasylyk ◽  
B Wasylyk
Keyword(s):  
Hela Cells ◽  
Serum Response Factor ◽  
Tumor Promoter ◽  
3T3 Cells ◽  
Carg Box ◽  
Specific Regulation ◽  
Nih 3T3 ◽  
Serum Response ◽  
Nih 3T3 Cells

We have identified oncogene-responsive sequences in the human c-fos promoter that mediate induction of transcription by several nonnuclear oncoproteins and the tumor promoter TPA. These sequences are regulated in a cell-specific manner. (i) In NIH 3T3 cells, the CArG box of the c-fos promoter is sufficient to mediate activation by oncogenes. (ii) In contrast, in HeLa cells, additional flanking sequences are also required, including the outer arm of the serum response element and the FAP site. We also show that the serum response factor, which binds to the CArG box, activates transcription in vivo in NIH 3T3 cells but not in HeLa cells. Finally, we present evidence that the intracellular level of the c-Fos protein could be a major determinant of cell-specific regulation of these oncogene-responsive elements of the c-fos promoter.

scholarly journals Regulatory role of MEF2D in serum induction of the c-jun promoter.

1995 ◽  
Vol 15 (6) ◽  
pp. 2907-2915 ◽  
Author(s):  
T H Han ◽  
R Prywes
Keyword(s):  
Dna Binding ◽  
Reporter Gene ◽  
Hela Cells ◽  
Serum Response Factor ◽  
Common Mechanism ◽  
Response Factor ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Serum Response ◽  
Nih 3T3 Cells

Serum induction of c-jun expression in HeLa cells requires a MEF2 site at -59 in the c-jun promoter. MEF2 sites, found in many muscle-specific enhancers, are bound by a family of transcription factors, MEF2A through -D, which are related to serum response factor in their DNA binding domains. We have found that MEF2D is the predominant protein in HeLa cells that binds to the c-jun MEF2 site. Serum induction of a MEF2 reporter gene was not observed in a line of NIH 3T3 cells which contain low MEF2 site binding activity. Transfection of MEF2D into NIH 3T3 cells reconstituted serum induction, demonstrating that MEF2D is required for the serum response. Deletion analysis of MEF2D showed that its DNA binding domain, when fused to a heterologous transcriptional activation domain, was sufficient for serum induction of a MEF2 reporter gene. This is the domain homologous to that in the serum response factor which is required for serum induction of the c-fos serum response element, suggesting that serum regulation of c-fos and c-jun may share a common mechanism.

scholarly journals Cell-specific regulation of oncogene-responsive sequences of the c-fos promoter.

1991 ◽  
Vol 11 (10) ◽  
pp. 5381-5387 ◽  
Author(s):  
A Gutman ◽  
C Wasylyk ◽  
B Wasylyk
Keyword(s):  
Hela Cells ◽  
Serum Response Factor ◽  
Tumor Promoter ◽  
3T3 Cells ◽  
Carg Box ◽  
Specific Regulation ◽  
Nih 3T3 ◽  
Serum Response ◽  
Nih 3T3 Cells

We have identified oncogene-responsive sequences in the human c-fos promoter that mediate induction of transcription by several nonnuclear oncoproteins and the tumor promoter TPA. These sequences are regulated in a cell-specific manner. (i) In NIH 3T3 cells, the CArG box of the c-fos promoter is sufficient to mediate activation by oncogenes. (ii) In contrast, in HeLa cells, additional flanking sequences are also required, including the outer arm of the serum response element and the FAP site. We also show that the serum response factor, which binds to the CArG box, activates transcription in vivo in NIH 3T3 cells but not in HeLa cells. Finally, we present evidence that the intracellular level of the c-Fos protein could be a major determinant of cell-specific regulation of these oncogene-responsive elements of the c-fos promoter.

scholarly journals Anticancer Effect of Hypophyllanthin, Niranthin and Lintetralin From Phyllanthus amarus on HeLa Cells And NIH/3T3 Cells

2019 ◽  
Vol 8 (2S7) ◽  
pp. 106-110
Keyword(s):  
Traditional Medicine ◽  
Hela Cells ◽  
Chemical Compounds ◽  
Phyllanthus Amarus ◽  
3T3 Cells ◽  
Anticancer Effect ◽  
Nih 3T3 ◽  
Mtt Assays ◽  
Nih 3T3 Cells

Phyllanthus amarus which is locally known as Dukung Anak was one of the herb used in traditional medicine and research of P. amarus in Malaysia was not widely reported. This present research has isolated three chemical compounds and its anticancer effect of this species has been determined. Three lignans namely hypophyllanthin was afforded from hexane crude while niranthin and lintetralin were afforded from ethanol crude. Anticancer test against HeLa cells and NIH/3T3 cells by MTT assays was tested for its anticancer effect. The result shows that hypophyllanthin was considered to possess an active anticancer effect on HeLa cells than NIH/3T3 cells compared to niranthin and lintetralin.

scholarly journals ΔRaf-1:ER* Bypasses the Cyclic AMP Block of Extracellular Signal-Regulated Kinase 1 and 2 Activation but Not CDK2 Activation or Cell Cycle Reentry

2003 ◽  
Vol 23 (24) ◽  
pp. 9303-9317 ◽  
Author(s):  
Kathryn Balmanno ◽  
Tracy Millar ◽  
Martin McMahon ◽  
Simon J. Cook
Keyword(s):  
Cell Cycle ◽  
Cyclic Amp ◽  
Dna Synthesis ◽  
Cyclin D1 ◽  
Cyclin A ◽  
3T3 Cells ◽  
Cell Cycle Reentry ◽  
Extracellular Signal ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Elevation of cellular cyclic AMP (cAMP) levels inhibits cell cycle reentry in a variety of cell types. While cAMP can prevent the activation of Raf-1 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by growth factors, we now show that activation of ERK1/2 by ΔRaf-1:ER is insensitive to cAMP. Despite this, ΔRaf-1:ER-stimulated DNA synthesis is still inhibited by cAMP, indicating a cAMP-sensitive step downstream of ERK1/2. Although cyclin D1 expression has been proposed as an alternative target for cAMP, we found that cAMP could inhibit ΔRaf-1:ER-induced cyclin D1 expression only in Rat-1 cells, not in CCl39 or NIH 3T3 cells. ΔRaf-1:ER-stimulated activation of CDK2 was strongly inhibited by cAMP in all three cell lines, but cAMP had no effect on the induction of p21CIP1. cAMP blocked the fetal bovine serum (FBS)-induced degradation of p27KIP1; however, loss of p27KIP1 in response to ΔRaf-1:ER was less sensitive in CCl39 and Rat-1 cells and was completely independent of cAMP in NIH 3T3 cells. The most consistent effect of cAMP was to block both FBS- and ΔRaf-1:ER-induced expression of Cdc25A and cyclin A, two important activators of CDK2. When CDK2 activity was bypassed by activation of the ER-E2F1 fusion protein, cAMP no longer inhibited expression of Cdc25A or cyclin A but still inhibited DNA synthesis. These studies reveal multiple points of cAMP sensitivity during cell cycle reentry. Inhibition of Raf-1 and ERK1/2 activation may operate early in G1, but when this early block is bypassed by ΔRaf-1:ER, cells still fail to enter S phase due to inhibition of CDK2 or targets downstream of E2F1.

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