Imatinib mesylate (IM)-induced growth inhibition is associated with production of spliced osteocalcin-mRNA in cell lines.
It has been suggested that imatinib mesylate (IM) influences osteogenesis and bone turnover in treated patients. Here we show that the inhibitory effect of IM on cell multiplication is associated with an increased proportion of spliced osteocalcin (OCNs) in leukemia (HL-60) and osteosarcoma cells (MG-63, U-2 OS), despite a lower mRNA synthesis rate. In mouse osteoblastic MC3T3-E1 cells only OCNs is present, independently of treatment. As the stimulatory effect of IM on OCNs is also observed upon treatment with vitamin D, common regulatory processes may be considered.
Wihlidal
Peter
P
Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria.
Karlic
Heidrun
H
Pfeilstöcker
Michael
M
Klaushofer
Klaus
K
Varga
Franz
F
D000818:Animals; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012326:RNA Splicing; D019098:Telomerase / Q000378:metabolism*