Regulation of BALB/c 3T3 fibroblast proliferation by B-myb is accompanied by selective activation of cdc2 and cyclin D1 expression.
The B-myb gene is expressed in many cell types at the G1/S transition of the cell cycle. Inhibition of B-myb expression in BALB/c 3T3 fibroblasts by introduction of a B-myb antisense construct greatly diminished cell proliferation, whereas constitutive expression of a human B-myb cDNA in these cells reduced their growth factor requirements and induced a transformed phenotype. Constitutive expression of B-myb cDNA was accompanied by activation of cyclin D1 and cdc2 expression but not of cyclin A and cyclin B. Transfection of BALB/B-myb cells (a cell line expressing high levels of exogenous human B-myb) with a cyclin D1 antisense construct drastically reduced cloning efficiency of these cells. These results suggest that the B-myb-encoded product regulates fibroblast proliferation by activating cdc2 and cyclin D1 gene expression and that abnormal expression of cyclin D1 might be a step in the process of transformation.
Sala
A
A
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107.
Calabretta
B
B
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D002455:Cell Division; D003001:Cloning, Molecular; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016213:Cyclins; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D020626:Oncogene Proteins v-myb; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase