Normal and transformed human prokeratinocytes express divergent effects of a tumor promoter on cell cycle-mediated control of proliferation and differentiation.
Normal and transformed human prokeratinocytes express divergent effects of a tumor promoter on cell cycle-mediated control of proliferation and differentiation.
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正常和转化的人原角质形成细胞表达肿瘤启动子对细胞周期介导的增殖和分化控制的不同作用。
DOI：
10.1093/carcin/6.8.1181
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发表时间：
1985
期刊：
影响因子：
4.7
通讯作者：
Scott,RE
中科院分区：
文献类型：
--
作者：
WilleJr,JJ;Pittelkow,MR;Scott,RE
肿瘤促进剂，12-O-十四烷酰基佛波醇-13-乙酸酯（TPA），被证明是一个有效的生长抑制剂的正常人前角质形成细胞（HPK）在无血清培养基中培养。更具体地，TPA以剂量依赖性方式抑制低密度HPK培养物的克隆生长，TPA的抗增殖作用是选择性的，因为无活性的佛波醇二酯，4-α-12，13-佛波醇二癸酸酯，不发挥类似的作用。一小时脉冲暴露于TPA的HPK也具有与连续暴露于TPA相当的效果;两种治疗均诱导快速生长停滞。流式细胞荧光分析的DNA含量表明，在TPA处理的HPK生长停滞与积累的细胞在G1和G2/M期的细胞周期。最有趣的是，数据确定TPA诱导的HPK生长停滞是不可逆的，因为处理的细胞失去了它们的集落形成潜力，并且当置于分化促进培养基中时，这些细胞致力于分化而没有进一步的细胞周期进展。相比之下，命名为SCC-25的人鳞状细胞癌细胞系对TPA的抗增殖作用不敏感，无论这些细胞是在含血清培养基还是无血清培养基中培养。这些数据被解释为表明，转化的人上皮细胞SCC-25是有缺陷的，他们的能力，以调节其增殖和分化的TPA敏感的细胞周期依赖性机制。
The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), is shown to be a potent inhibitor of growth of normal human prokeratinocytes (HPK) cultured in serum-free medium. More specifically TPA inhibits the clonal growth of low density HPK cultures in a dose-dependent manner and the anti-proliferative effect of TPA is selective in that the inactive phorbol diester, 4-α-12, 13-phorbol didecanoate, does not exert a similar effect. One-hour pulse exposure of HPK to TPA also has an effect comparable with continuous exposure to TPA; both treatments induce rapid growth arrest. Flow cytofluorometric analysis of DNA content shows that in TPA-treated HPK growth arrest is associated with accumulation of cells in both the G1and G2/Mphases of the cell cycle. Most interestingly, the data establish that the growth arrest of HPK induced by TPA is irreversible in that treated cells lose their colony-forming potential and that such cells are committed to differentiate without further cell cycle progression when placed in differentiation-promoting medium. In contrast, a human squamous carcinoma cell line, designated SCC-25, is insensitive to the anti-proliferative effect of TPA regardless of whether these cells are cultured in either serum-containing or serum-free medium. These data are interpreted to suggest that transformed human epithelial cells SCC-25 are defective in their ability to regulate their proliferation and differentiation by TPA-sensitive cell cycle-dependent mechanisms.