Herschman H R, Brankow D W
Carcinogenesis. 1987 Jul;8(7):993-8. doi: 10.1093/carcin/8.7.993.
UV-TDTx cells are cloned from foci arising after C3H10T1/2 cells are sequentially exposed to u.v. irradiation followed by tetradecanoylphorbol acetate (TPA). When grown in pure culture, UV-TDTx cells appear transformed. Co-culture with C3H10T1/2 cells suppresses focus formation by the UV-TDTx cells. In the presence of TPA, however, focus formation by UV-TDTx cells occurs in C3H10T1/2 co-cultures. We now demonstrate that only tumor promoters that activate protein kinase C (TPA, teleocidin) can reverse C3H10T1/2 suppression of UV-TDTx focus formation in co-culture; other promoters (diethyl stilbestrol, dioxin, saccharin, cadmium) are inactive. Retinoic acid, a potent inhibitor of many biological effects of TPA, blocks the action of TPA in UV-TDTx:C3H10T1/2 co-cultures. Focus formation by UV-TDTx cells in co-culture is dependent on the size of the UV-TDTx colony at confluence; if the UV-TDTx colony is below a minimal size when the co-cultures reach density-dependent growth arrest, suppression of focus formation by C3H10T1/2 cells occurs even in the presence of TPA. Finally, TPA must be present prior to confluence to relieve suppression of focus formation. If TPA is added to co-cultures after density arrest, UV-TDTx cells will not subsequently form foci.
UV - TDTx细胞是从C3H10T1/2细胞先后经紫外线照射和十四酰佛波醇乙酸酯（TPA）处理后出现的病灶中克隆而来的。在纯培养中生长时，UV - TDTx细胞呈现出转化状态。与C3H10T1/2细胞共培养会抑制UV - TDTx细胞的病灶形成。然而，在TPA存在的情况下，UV - TDTx细胞在与C3H10T1/2细胞的共培养中会形成病灶。我们现在证明，只有激活蛋白激酶C的肿瘤启动子（TPA、远藤霉素）能够逆转C3H10T1/2细胞在共培养中对UV - TDTx病灶形成的抑制作用；其他启动子（己烯雌酚、二噁英、糖精、镉）则无活性。视黄酸是TPA许多生物学效应的有效抑制剂，它会阻断TPA在UV - TDTx:C3H10T1/2共培养中的作用。UV - TDTx细胞在共培养中的病灶形成取决于汇合时UV - TDTx集落的大小；如果在共培养达到密度依赖性生长停滞时UV - TDTx集落低于最小尺寸，即使在TPA存在的情况下，C3H10T1/2细胞对病灶形成的抑制作用仍会发生。最后，TPA必须在汇合前存在才能解除对病灶形成的抑制。如果在密度停滞后将TPA添加到共培养物中，UV - TDTx细胞随后将不会形成病灶。
