Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevation of the steady-state mRNA levels of glucose transporter and c-myc are among the earliest changes in gene expression observed after Ha-rasT24 stimulation of Rat-1 fibroblasts to enter the cell cycle. Since the expression of these genes may be the result of either increased cell proliferation or a specific response to rasT24, we evaluated the expression of glucose transporter and c-myc and their induction during the cell cycle in both parental Rat-1 cells and cell lines bearing a metallothionein rasT24 fusion gene (MTrasT24). We showed that, although levels of glucose transporter and c-myc mRNAs in Rat-1 cells underwent a transient increase within hours of the addition of serum, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate to quiescent (G0) cells, the levels of glucose transporter and c-myc mRNA otherwise remained constant throughout the normal cell cycle. In cells carrying MTrasT24 (MR5 cells), induction of rasT24 expression by ZnSO4 led to a rapid induction of glucose transporter and c-myc mRNA expression in both quiescent (density-arrested) and G1/S-synchronized (aphidicolin-blocked) cells. These increases exceeded the constitutive levels expressed in rapidly proliferating Rat-1 cells, indicating that the ras oncogene has an effect on these genes that is independent of growth status. In addition, the transin gene, which is not expressed in proliferating Rat-1 cells in the continuous presence of serum growth factors, was also induced after increased expression of the mutant ras gene. These results suggest that the induction of glucose transporter, c-myc, and transin is the direct result of rasT24-mediated alterations in cellular gene expression and is distinct from normal cell-cycle events.
 ...
PMID:Elevation of glucose transporter, c-myc, and transin RNA levels by Ha-rasT24 is independent of its effect on the cell cycle. 187 50

We have used a series of Rat-1 cell lines carrying a Zn-inducible human c-Ha-ras oncogene construction (MTrasT24) to evaluate the effect of varied ras oncogene expression on the expression of genes and proteins related to morphologic transformation in vitro. In response to the expression of the ras oncogene, at least two different classes of events occur. These events, referred to as 'early and late' events, are dependent on distinctively different accumulated levels of the ras oncoprotein. Relatively low levels of activated c-Ha-ras p21 protein (1.5-2.5 times the proto-oncogene level) stimulate rapid entry of quiescent (G0) cells into the cell cycle and result in increased steady state c-myc and glucose transporter mRNA levels which are detectable as early as 3-6 h after zinc addition. In contrast, morphologic transformation develops more slowly and does not appear until 72-96 h after Zn++ stimulation in cells with very low basal levels of activated p21 (MR4 cells) and 24-48 h in cells with higher basal levels (MR5 cells). These morphologic changes depend on the accumulation of significant amounts of the ras oncoprotein (greater than 4 to 5 times the proto-oncogene level) and are accompanied by large increases in the steady state mRNA levels of transin and TGF-alpha and decreases in PDGF-receptor mRNA and fibronectin protein and mRNA levels. In addition, the level of a novel cytoplasmic protein species (referred to as p29), which is stained by a monoclonal antibody for ras, is dramatically reduced in response to these levels of activated ras protein. Thus changes in morphology and gene expression induced by rasT24 occur sequentially and are quantitatively dependent on activated ras expression.
 ...
PMID:Early and late responses to induction of rasT24 expression in Rat-1 cells. 220 52

We have studied the effects of c-Ha-ras oncogene in mouse NIH 3T3 fibroblasts by DNA transfection and analysis of gene expression at the mRNA and protein level in a heat- and heavy metal-inducible model system. The human c-Ha-ras proto-oncogene and oncogene were cloned under the hsp70 heat-shock promoter. Clonal lines of cells with negligible basal expression of the hsp-c-Ha-ras oncogene construct were chosen on the basis of the inducibility of p21c-Ha-ras protein and several transformation parameters. We demonstrate that the expression of ornithine decarboxylase (ODC) mRNA is enhanced approximately 4-6 h after the induction of the p21c-Ha-ras oncoprotein. This increase was reversible upon cessation of c-Ha-ras mRNA and protein synthesis, while constitutively elevated ODC was characteristic for stably c-Ha-ras-transformed cells. The high-level expression of ODC in ras-transformed cells was insensitive to tumour promoter stimulation. A similar mRNA induction by c-Ha-rasVal-12 was also observed for two other serum- and tumour promoter-regulated genes associated with the transformed phenotype: transin (stromelysin) and the glucose transporter. This prompted us to examine also potential changes in the expression of the serum- and tumour promoter-induced transcription factor genes junB and c-jun after induction of the hsp--c-Ha-ras construct. The junB mRNA was enhanced approximately 10-fold and the c-jun oncogene mRNA to a lesser degree in the hsp--c-Ha-ras-transfected cells after zinc activation of the hsp70 promoter. These effects were not seen in similarly treated control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The cellular response to induction of the p21 c-Ha-ras oncoprotein includes stimulation of jun gene expression. 249 84