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Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes
Abstract:
An accelerated rate of glucose transport is among the most characteristic biochemical markers of cellular transformation. To study the molecular mechanism by which transporter activity is altered, cultured rodent fibroblasts transfected with activated myc, ras, or src oncogenes were used. In myc-transfected cells, the rate of 2-deoxy-D-glucose uptake was unchanged. However, in cells transfected with activated ras and src oncogenes, the rate of glucose uptake was markedly increased. The increased transport rate in ras- and src-transfected cells was paralleled by a marked increase in the amount of glucose transporter protein, as assessed by immunoblots, as well as by a markedly increased abundance of glucose transporter messenger RNA. Exposure of control cells to the tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) for 18 hours had a similar effect of increasing the rate of glucose transport and the abundance of transporter messenger RNA. For ras, src, and TPA, the predominant mechanism responsible for activation of the transport system is increased expression of the structural gene encoding the glucose transport protein.
Insights
Activated ras and src oncogenes increase glucose transport in fibroblasts by upregulating glucose transporter gene expression. This mechanism, similar to TPA effects, is key to cellular transformation.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Accelerated glucose transport is a hallmark of cellular transformation.
- Understanding the molecular mechanisms behind altered transporter activity is crucial.
Purpose of the Study:
- To investigate how activated oncogenes (myc, ras, src) affect glucose transport rates and mechanisms in cultured rodent fibroblasts.
- To determine if increased glucose transport is linked to oncogene-induced cellular changes.
Main Methods:
- Fibroblasts were transfected with activated myc, ras, or src oncogenes.
- Glucose uptake rates were measured using 2-deoxy-D-glucose.
- Glucose transporter protein levels were assessed via immunoblotting.
- Glucose transporter messenger RNA abundance was quantified.
Main Results:
- Activated ras and src oncogenes significantly increased glucose uptake rates.
- This increase correlated with elevated glucose transporter protein and messenger RNA levels.
- Activated myc oncogene did not alter glucose uptake.
- Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) mimicked the effects of ras and src.
Conclusions:
- Increased glucose transporter gene expression is the primary mechanism driving enhanced glucose transport in ras- and src-transformed cells.
- This upregulation is a key event in oncogene-mediated cellular transformation.
- The findings highlight a common pathway involving gene expression for oncogenic activation of glucose transport.