Wilson V L, Masui T, Smith R A, Harris C C
Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892.
Carcinogenesis. 1988 Dec;9(12):2155-9. doi: 10.1093/carcin/9.12.2155.
The terminal squamous differentiation of epithelial cells involves a number of cellular changes. However, the mechanisms underlying this differentiation process are unknown. The present study demonstrates that 5-azacytidine, 12-O-tetradecanoylphorbol-13-acetate (TPA) and type beta-transforming growth factor (TGF-beta) significantly diminish the genomic 5-methyldeoxycytidine (5mdC) content of normal human bronchial epithelial cells concomitantly with the induction of squamous differentiation. 5-Azacytidine or TPA, but not type beta-transforming growth factor, also initiated decreases in the genomic 5mdC content of differentiation nonresponsive human tumor A549 cells. These effects of TPA or type beta-transforming growth factor occurred at concentrations of 1 nM and 1.2 pM, respectively, which were approximately one tenth of kd values of their specific receptors. Therefore, the decreases in genomic 5mdC induced by these agents were probably mediated, directly or indirectly, by receptor--ligand interactions.
上皮细胞的终末鳞状分化涉及许多细胞变化。然而，这种分化过程背后的机制尚不清楚。本研究表明，5-氮杂胞苷、12-O-十四酰佛波醇-13-乙酸酯（TPA）和β型转化生长因子（TGF-β）在诱导鳞状分化的同时，显著降低正常人支气管上皮细胞的基因组5-甲基脱氧胞苷（5mdC）含量。5-氮杂胞苷或TPA，但不是β型转化生长因子，也引发了对分化无反应的人肿瘤A549细胞基因组5mdC含量的降低。TPA或β型转化生长因子的这些作用分别在1 nM和1.2 pM的浓度下出现，这大约是它们特异性受体kd值的十分之一。因此，这些试剂诱导的基因组5mdC的降低可能直接或间接地由受体-配体相互作用介导。
