Expression of the high mobility group A family member p8 is essential to maintaining tumorigenic potential by promoting cell cycle dysregulation in LbetaT2 cells.
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.
Brannon
K M
KM
Department of Biology, Indiana University, Bloomington, IN 47405-4401, USA.
Million Passe
C M
CM
White
C R
CR
Bade
N A
NA
King
M W
MW
Quirk
C C
CC
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D024003:HMGA Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004268:DNA-Binding Proteins; D024003:HMGA Proteins; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D001616:beta-Galactosidase