Retinoids enhance lectin binding to gp130, a glycoprotein of NIH-3T3 cells: Correlation with cell growth and adhesion

ABSTRACT The GTPase-deficient, activated mutant of Gα12 (Gα12Q229L, or Gα12QL) induces neoplastic growth and oncogenic transformation of NIH 3T3 cells. Using microarray analysis, we have previously identified a role for platelet-derived growth factor receptor α (PDGFRα) in Gα12-mediated cell growth (R. N. Kumar et al., Cell Biochem. Biophys. 41:63-73, 2004). In the present study, we report that Gα12QL stimulates the functional expression of PDGFRα and demonstrate that the expression of PDGFRα by Gα12QL is dependent on the small GTPase Rho. Our results indicate that it is cell type independent as the transient expression of Gα12QL or the activation of Gα12-coupled receptors stimulates the expression of PDGFRα in NIH 3T3 as well as in human astrocytoma 1321N1 cells. Furthermore, we demonstrate the presence of an autocrine loop involving PDGF-A and PDGFRα in Gα12QL-transformed cells. Analysis of the functional consequences of the Gα12-PDGFRα signaling axis indicates that Gα12 stimulates the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway through PDGFR. In addition, we show that Gα12QL stimulates the phosphorylation of forkhead transcription factor FKHRL1 via AKT in a PDGFRα- and PI3K-dependent manner. Since AKT promotes cell growth by blocking the transcription of antiproliferative genes through the inhibitory phosphorylation of forkhead transcription factors, our results describe for the first time a PDGFRα-dependent signaling pathway involving PI3K-AKT-FKHRL1, regulated by Gα12QL in promoting cell growth. Consistent with this view, we demonstrate that the expression of a dominant negative mutant of PDGFRα attenuated Gα12-mediated neoplastic transformation of NIH 3T3 cells.

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Stimulation of cell growth and proliferation in NIH-3T3 cells by onion and garlic oils

Cell Biology and Toxicology ◽

10.1007/bf00121852 ◽

1986 ◽

Vol 2 (3) ◽

pp. 369-378 ◽

Cited By ~ 5

Author(s):

Judith T. Zelikoff ◽

Norman M. Atkins ◽

Sidney Belman

Keyword(s):

Cell Growth ◽

3T3 Cells ◽

Cell Growth And Proliferation ◽

Nih 3T3 ◽

Stimulation Of ◽

Nih 3T3 Cells

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

Molecular and Cellular Biology ◽

10.1128/mcb.22.11.3717-3728.2002 ◽

2002 ◽

Vol 22 (11) ◽

pp. 3717-3728 ◽

Cited By ~ 55

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.

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The effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on cell growth, cell cycle, induction of DNA fragmentation, and activity of caspase 3 in murine leukemia L1210 cells and fibroblast NIH-3T3 cells

Cell Biochemistry and Function ◽

10.1002/cbf.1296 ◽

2006 ◽

Vol 24 (6) ◽

pp. 519-530 ◽

Cited By ~ 10

Author(s):

S. Jantová ◽

S. Letašiová ◽

A. Repický ◽

R. Ovádeková ◽

B. Lakatoš

Keyword(s):

Cell Cycle ◽

Cell Growth ◽

Dna Fragmentation ◽

Caspase 3 ◽

3T3 Cells ◽

L1210 Cells ◽

Nih 3T3 ◽

Murine Leukemia ◽

Nih 3T3 Cells

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Depletion of Mammalian CCR4b Deadenylase Triggers Elevation of the p27Kip1 mRNA Level and Impairs Cell Growth

Molecular and Cellular Biology ◽

10.1128/mcb.02304-06 ◽

2007 ◽

Vol 27 (13) ◽

pp. 4980-4990 ◽

Cited By ~ 79

Author(s):

Masahiro Morita ◽

Toru Suzuki ◽

Takahisa Nakamura ◽

Kazumasa Yokoyama ◽

Takashi Miyasaka ◽

...

Keyword(s):

Cell Growth ◽

Mrna Level ◽

3T3 Cells ◽

Cellular Events ◽

The Stability ◽

Nih 3T3 ◽

Nih 3T3 Cells

ABSTRACT The stability of mRNA influences the abundance of cellular transcripts and proteins. Deadenylases play critical roles in mRNA turnover and thus are important for the regulation of various biological events. Here, we report the identification and characterization of CCR4b/CNOT6L, which is homologous to yeast CCR4 mRNA deadenylase. CCR4b is localized mainly in the cytoplasm and displays deadenylase activity both in vitro and in vivo. CCR4b forms a multisubunit complex similar to the yeast CCR4-NOT complex. Suppression of CCR4b by RNA interference results in growth retardation of NIH 3T3 cells accompanied by elevation of both p27 Kip1 mRNA and p27Kip1 protein. Reintroduction of wild-type CCR4b, but not mutant CCR4b lacking deadenylase activity, restores the growth of CCR4b-depleted NIH 3T3 cells. The data suggest that CCR4b regulates cell growth in a manner dependent on its deadenylase activity. We also show that p27 Kip1 mRNA is stabilized and its poly(A) tail is preserved in CCR4b-depleted cells. Our findings provide evidence that CCR4b deadenylase is a constituent of the mammalian CCR4-NOT complex and regulates the turnover rate of specific target mRNAs. Thus, CCR4b may be involved in various cellular events that include cell proliferation.

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Regulation of the expression of cyclin-dependent kinase inhibitor p21 by E2A and Id proteins.

Molecular and Cellular Biology ◽

10.1128/mcb.17.10.5888 ◽

1997 ◽

Vol 17 (10) ◽

pp. 5888-5896 ◽

Cited By ~ 226

Author(s):

S Prabhu ◽

A Ignatova ◽

S T Park ◽

X H Sun

Keyword(s):

Cell Growth ◽

Kinase Inhibitor ◽

Control Cell ◽

Luciferase Reporter ◽

Cyclin Dependent Kinase ◽

3T3 Cells ◽

Cyclin Dependent Kinase Inhibitor ◽

Id Proteins ◽

Nih 3T3 ◽

Nih 3T3 Cells

The helix-loop-helix transcription factor E2A plays important roles not only in promoting cellular differentiation but also in suppressing cell growth. Id proteins, the inhibitors of E2A, have opposite effects on cell differentiation and growth. To understand the mechanisms by which E2A suppresses cell growth, we examined the role of E2A in regulating the expression of the cyclin-dependent kinase inhibitor p21CIP1/WAF1/SD11, which prevents cell cycle progression upon overexpression. By using transient-cotransfection assays of luciferase reporter constructs in HeLa cells, we have found that overexpression of E2A can transcriptionally activate the p21 gene. To identify the sequences that mediate this activation in the promoter of the p21 gene, we carried out mutational analyses. Out of the eight putative E2A-binding sequences (E1 to E8) in the promoter, the E1 to E3 sequences located close to the transcription start site are found to be essential. In addition, loss of the E boxes in the promoter also reduces p21 expression without cotransfection with E2A in HIT pancreatic cells, where the endogenous E2A-like activity is high. Furthermore, we have also shown that overexpression of E2A in 293T cells activates expression of the endogenous p21 gene at both the levels of mRNA and protein. In correlation with the finding that E47 overexpression leads to growth arrest in NIH 3T3 cells, we have shown that Id1 overexpression in NIH 3T3 cells accelerates cell growth and inhibits p21 expression. Taken together, these results provide insight into the mechanisms by which E2A and Id proteins control cell growth.

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