Albright Craig D, Grimley Philip M, Jones Raymond T, Resau James H
Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Exp Mol Pathol. 2002 Feb;72(1):62-7. doi: 10.1006/exmp.2001.2411.
Understanding how normal and immortalized bronchial epithelial cells respond to modulators of gap junctional communication will increase our understanding of the process of tumor promotion. In the present study we compared to effects of retinoic acid (RA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the rate of fluorescent dye transfer via gap junctions in primary human tracheo-bronchial epithelial cells (TBE) and SV40 large T-antigen immortalized, non-tumorigenic bronchial epithelial cells (BEAS-2B). RA in the physiological range (0.001-1 microM) inhibited cell proliferation (DNA synthesis, mitotic index) more in primary TBE cells than BEAS-2B cells. Also in RA-treated cells, decreased cell proliferation was coupled to decreased gap junctional communication (GJC) in TBE but not in BEAS-2B cells. TPA strongly suppressed GJC and proliferation in primary TBE cells, whereas BEAS-2B exhibited increased GJC and retained a significant fraction of cells undergoing DNA synthesis. Our studies show that an uncoupling of GJC and cell proliferation is associated with a differential response to the growth inhibitory effects of RA and phorbol esters in immortalized compared to primary human bronchial epithelial cells.
了解正常和永生化支气管上皮细胞如何对间隙连接通讯调节剂作出反应，将增进我们对肿瘤促进过程的理解。在本研究中，我们比较了视黄酸（RA）和12-O-十四烷酰佛波醇-13-乙酸酯（TPA）对原代人气管支气管上皮细胞（TBE）和SV40大T抗原永生化、非致瘤性支气管上皮细胞（BEAS-2B）中荧光染料通过间隙连接的转移速率的影响。生理范围内（0.001 - 1 microM）的RA对原代TBE细胞的细胞增殖（DNA合成、有丝分裂指数）的抑制作用比对BEAS-2B细胞更强。同样在经RA处理的细胞中，TBE细胞中细胞增殖的降低与间隙连接通讯（GJC）的降低相关，但在BEAS-2B细胞中并非如此。TPA强烈抑制原代TBE细胞中的GJC和增殖，而BEAS-2B细胞则表现出GJC增加，并且有相当一部分细胞仍在进行DNA合成。我们的研究表明，与原代人支气管上皮细胞相比，永生化细胞中GJC与细胞增殖的解偶联与对RA和佛波酯生长抑制作用的不同反应有关。
