Leinonen P, Alhonen-Hongisto L, Laine R, Jänne O A, Jänne J
FEBS Lett. 1987 May 4;215(1):68-72. doi: 10.1016/0014-5793(87)80115-1.
Chronic exposure of a human myeloma cell line to dexamethasone resulted in a selection of cells resistant to the growth-inhibitory action of the glucocorticoid. Upon acute exposure of the parental myeloma cells to dexamethasone growth inhibition was associated with depression of ornithine decarboxylase (ODC, EC 4.1.1.17) activity. However, in cells adapted to grow in the presence of micromolar concentrations of dexamethasone, ODC activity was fully comparable to that in the parental cells. Restriction enzyme analyses with the two isoschizomers HpaII and MspI as well as with the methylation-sensitive CfoI, indicated that the otherwise heavily methylated ODC gene(s) were rendered hypomethylated in the myeloma cells resistant to dexamethasone. This hypomethylation within and/or around ODC genes was associated with a 2-4-fold enhancement of accumulation of ODC mRNA.
将人骨髓瘤细胞系长期暴露于地塞米松会导致选择出对糖皮质激素生长抑制作用具有抗性的细胞。亲代骨髓瘤细胞急性暴露于地塞米松时，生长抑制与鸟氨酸脱羧酶（ODC，EC 4.1.1.17）活性降低相关。然而，在适应于在微摩尔浓度地塞米松存在下生长的细胞中，ODC活性与亲代细胞中的完全相当。用两种同裂酶HpaII和MspI以及对甲基化敏感的CfoI进行的限制性酶切分析表明，原本高度甲基化的ODC基因在对地塞米松有抗性的骨髓瘤细胞中变得低甲基化。ODC基因内部和/或周围的这种低甲基化与ODC mRNA积累增加2至4倍相关。
