Zhang H, Koty P P, Mayotte J, Levitt M L
Lung Cancer Program, Allegheny University of the Health Sciences-Allegheny Campus, Pittsburgh, Pennsylvania, 15212, USA.
Exp Cell Res. 1999 Feb 25;247(1):133-41. doi: 10.1006/excr.1998.4329.
Tissue transglutaminase (tTG) and keratinocyte transglutaminase (kTG), as well as the cross-linked envelopes (CLE) that they form, have been associated with squamous differentiation and programmed cell death in epithelial cells. When interferon-beta (IFN-beta) was used to stimulate differentiation and programmed cell death in the human lung cancer cell lines NCI-H596 and NCI-H226, the cells underwent a decrease in cellular density. In NCI-H596 IFN-beta caused an increase in kTG activity and DNA fragmentation in the lower density cells, which were significantly slower growing than control cells. However, in the higher density cells, which were only slightly slower growing than control cells, IFN-beta caused an increase in tTG activity and CLE competence. Dual-parameter flow cytometry demonstrated that IFN-beta-induced squamous differentiation preceded programmed cell death. Treatment of NCI-H596 cells with monodansylcadaverine, a transglutaminase inhibitor, prevented the increase in CLE competence, but did not inhibit DNA fragmentation. These results suggest that IFN-beta can induce NCI-H596 cells to enter multiple cell death pathways and that these pathways are not only differentiation related, but may also be growth driven.
组织转谷氨酰胺酶（tTG）和角质形成细胞转谷氨酰胺酶（kTG），以及它们形成的交联包膜（CLE），与上皮细胞中的鳞状分化和程序性细胞死亡有关。当使用β-干扰素（IFN-β）刺激人肺癌细胞系NCI-H596和NCI-H226的分化和程序性细胞死亡时，细胞的细胞密度降低。在NCI-H596细胞中，IFN-β导致低密度细胞中kTG活性增加和DNA片段化，这些低密度细胞的生长速度明显慢于对照细胞。然而，在生长速度仅略慢于对照细胞的高密度细胞中，IFN-β导致tTG活性增加和CLE能力增强。双参数流式细胞术表明，IFN-β诱导的鳞状分化先于程序性细胞死亡。用转谷氨酰胺酶抑制剂单丹磺酰尸胺处理NCI-H596细胞，可阻止CLE能力的增加，但不抑制DNA片段化。这些结果表明，IFN-β可诱导NCI-H596细胞进入多种细胞死亡途径，且这些途径不仅与分化有关，还可能受生长驱动。
