Proteins involved in cellular growth signal transduction processes and their possible use as epidemiological biomarkers for various disease processes were discussed. The general characteristics of cell signal transduction processes were described. A typical growth signal transduction pathway involves a growth factor in the extracellular environment, a growth factor receptor on the cell membrane, G-proteins in the cytoplasm, and nuclear DNA binding proteins in the nucleus. The available evidence indicates that altered expression of the proteins involved in signal transduction, usually manifested as increases in amount or the occurrence of mutated forms, may serve as molecular biomarkers of signal transductions that have been disrupted or are malfunctioning, such as during carcinogenesis. Since these proteins can gain access to the extracellular environment, it should be possible to detect increased expression or expression of mutated forms of signal transduction pathways in serum, plasma, or urine. The use of specific proteins involved in signal transduction as biomarkers for disease conditions was discussed. Elevated plasma concentrations of platelet derived growth factor have been found in hepatocellular carcinoma and female breast cancer patients. Elevated serum G- protein concentrations have been found in patients with cancers of various types or in persons at risk for developing cancer because of carcinogenic exposures. Elevated concentrations of a specific ras gene mutation at codon 13 of the K-ras gene have been found in 83% of the patients with liver angiosarcoma caused by exposure to vinyl- chloride (75014). p53 mutations have been found in the sera of patients with a variety of cancers.
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