Abstract
The mechanism by which the HMGA protein p8 facilitates tumorigenesis may be cell cycle dysregulation. Control- (C) LbetaT2 cells, which express p8, form tumors at a rate five-times faster than p8-knockdown (p8-KD)-LbetaT2 cells. In association with this heightened tumorigenic potential, p8-expressing C-LbetaT2 cells avoid G(0)/G(1) arrest and become genetically unstable while p8-KD-LbetaT2 cells arrest in G(0)/G(1), become senescent upon overgrowth, and maintain a diploid population. These phenotypic changes correspond to altered cell cycle regulation at the G(1)-to-S transition that may be due to p8-mediated changes in expression of the Cip/Kip family members of cell cycle inhibitors, p21, p27, and p57.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cell Cycle / genetics*
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Cell Cycle / physiology
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Cell Line, Transformed
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Cell Proliferation
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Cellular Senescence / genetics
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Cellular Senescence / physiology
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Cyclin-Dependent Kinase Inhibitor p57 / genetics
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Cyclin-Dependent Kinase Inhibitor p57 / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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G1 Phase / genetics
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G1 Phase / physiology
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Gene Expression
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HMGA Proteins / genetics
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HMGA Proteins / metabolism
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Mice
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Mice, Nude
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Mutation
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology*
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Oligonucleotide Array Sequence Analysis
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Resting Phase, Cell Cycle / genetics
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Resting Phase, Cell Cycle / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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beta-Galactosidase / metabolism
Substances
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Cdkn1a protein, mouse
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Cdkn1b protein, mouse
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Cdkn1c protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p57
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DNA-Binding Proteins
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HMGA Proteins
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Neoplasm Proteins
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Nupr1 protein, mouse
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Cyclin-Dependent Kinase Inhibitor p27
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beta-Galactosidase