PubMed · 6493083
Three steps mutation model of carcinogenesis.
Abstract
Based on recent data, this model supposes that benign and malignant tumors arise when a specific mutation takes place in a specific protein-kinase encoded by a proto-oncogene in a pluripotent stem cell or a committed stem cell. Protein-kinases which are regulated by tissue growth stimulating factors, tissue growth inhibiting factors and differentiating factors phosphorylate specific proteins that can derepress specific genes leading to cell division and cell differentiation. Malignant tumors arise when three mutations happen in a same pluripotent stem cell or committed stem cell: positive mutation at the level of tissue growth stimulating factor; negative mutation at the level of tissue growth inhibiting factor; negative mutation at the level of tissue differentiating factor. Higher expression of oncogenes and amplification reflect the relationship between tumor and host. Chromosomal rearrangements are secondary events that can be important because they may involve genes which are normally not involved in cell division and cell differentiation.
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M De Braekeleer. 1984. Three steps mutation model of carcinogenesis.. https://doi.org/10.1016/0306-9877(84)90142-7
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