Abstract
Although great progress has been made at identifying and characterizing individual genes involved in cancer, less is known about how the combination of such genes collaborate to form tumors in humans. To this end, we sought to genetically recreate tumorigenesis in normal human cells using genes altered in human cancer. We now show that expression of mammalian proteins that inactivate the tumor suppressors Rb and p53 in conjunction with the oncoproteins Ras and Myc and the telomerase subunit hTERT is sufficient to drive a number of normal human somatic cells to a tumorigenic fate. This provides a blueprint of the events that lead to human cancer, allowing different cancers to be genetically modeled from normal human cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism
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Cyclin D1 / biosynthesis
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Cyclin D1 / genetics
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DNA-Binding Proteins / genetics
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Female
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Humans
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Mammary Glands, Human / cytology
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Mammary Glands, Human / metabolism
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Mammary Glands, Human / pathology
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Mammary Glands, Human / physiology*
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Mice
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / physiology
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / genetics
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Retinoblastoma Protein / biosynthesis
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Retinoblastoma Protein / genetics
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Telomerase / biosynthesis
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Telomerase / genetics
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
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ras Proteins / biosynthesis
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ras Proteins / genetics
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins c-myc
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Retinoblastoma Protein
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TP53 protein, human
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Tumor Suppressor Protein p53
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Cyclin D1
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Telomerase
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ras Proteins