Tumorigenicity and gene amplification potentials of cyclin D1-overexpressing NIH3T3 cells.
Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene is amplified and overexpressed in many cancers. To address the gene amplification potential of the cells in which the cyclin D1 gene expression is deregulated, we have established NIH3T3 clones with various levels of cyclin D1 transgene message. Those transfectants showed anchorage independent growth and tumorigenicity without in vitro morphological transformation. The degree of the transformed phenotype apparently correlated with the cyclin D1 expression level. Upon selection by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1-transfected NIH3T3 cells showed a higher ability to develop PALA-resistant colonies by amplifying the CAD gene, as compared to the parental NIH3T3 cells.
Asano
K
K
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Sakamoto
H
H
Sasaki
H
H
Ochiya
T
T
Yoshida
T
T
Ohishi
Y
Y
Machida
T
T
Kakizoe
T
T
Sugimura
T
T
Terada
M
M
D016475:3T3 Cells; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D004080:Dihydroorotase / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection
C033626:CAD trifunctional enzyme; D016213:Cyclins; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; D019938:Cyclin D1; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid