Chromosomal instability induced by Pim-1 is passage-dependent and associated with dysregulation of cyclin B1.
Overexpression of the oncogenic serine/threonine kinase Pim-1 has been shown to induce chromosomal missegregation and polyploidy in prostate epithelial cell lines (1). Here we demonstrated that Pim-1-induced polyploidy develops in a passage-dependent manner in culture consistent with a stochastic mode of progression. Induction of chromosomal instability by Pim-1 was not restricted to prostate cells as it was also observed in telomerase-immortalized normal human mammary epithelial cells. Elevated levels of cyclin B1 protein, but not its messenger RNA, were evident in early passage Pim-1 overexpressing cells, suggesting that increased cyclin B1 levels contribute to the development of polyploidy. Furthermore, regulation of cyclin B1 protein and cyclin B1/CDK1 activity after treatment with anti-microtubule agents was impaired. Small interfering RNA targeting cyclin B1 reversed the cytokinesis delay but not the mitotic checkpoint defect in Pim-1 overexpressing cells. These results indicated that chronic Pim-1 overexpression dysregulates cyclin B1 protein expression, which contributes to the development of polyploidy by delaying cytokinesis.
Roh
Meejeon
M
Department of Pathology, The University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama 35294, USA.
Song
Chisu
C
Kim
Jongchan
J
Abdulkadir
Sarki A
SA
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000187:drug effects*; D019926:Cyclin B / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D056744:Cyclin B1; D048749:Cytokinesis; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D011123:Polyploidy; D011471:Prostatic Neoplasms; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D034741:RNA, Small Interfering; D051573:Proto-Oncogene Proteins c-pim-1; D016203:CDC2 Protein Kinase; D015739:Nocodazole