Differential effects of tumor promoters on P210bcr-abl expression.
It is a widely held theory that the bcr-abl hybrid gene plays an active role in chronic myelogenous leukemia (CML). The bcr-abl gene product (P210bcr-abl) is a structurally altered and enzymatically activated form of the normal c-abl gene product. P210bcr-abl is expressed in two cell lines derived from CML patients in blast crisis: K562 and EM2. Activation of protein kinase C by the strong tumor promoter TPA induced dramatic changes in K562 cells. We have shown that exposure of K562 cells to low concentrations (10 nM) of TPA stopped cell division and sharply reduced the expression of P210bcr-abl. In contrast, similar treatment of EM2 cells resulted in a slightly increased proliferation rate and stimulation of P210bcr-abl expression. A second tumor promoter, mezerein, also dramatically reduced P210 levels in K562 cells and elevated them in EM2 cells. These observations establish that expression of the bcr-abl gene can be either increased or decreased, depending on the cell type, and that these effects correlate with the proliferative state of the cell. These results are consistent with the hypothesis that P210bcr-abl plays an important role in the maintenance of CML.
Li
W J
WJ
Johnson & Johnson Biotechnology Center, La Jolla, California 92037.
Smith
L A
LA
Kabat
K G
KG
Kloetzer
W S
WS
Arlinghaus
R B
RB
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D016044:Fusion Proteins, bcr-abl; D013755:Tetradecanoylphorbol Acetate