KLF4 and KLF5 regulate proliferation, apoptosis and invasion in Esophageal cancer cells
KLF4 and KLF5 regulate proliferation, apoptosis and invasion in Esophageal cancer cells
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DOI：
10.4161/cbt.4.11.2090
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发表时间：
2005-11-01
影响因子：
3.6
通讯作者：
Katz, JP
中科院分区：
文献类型：
--
作者：
Yang, YZ;Goldstein, BG;Katz, JP
KLF 4和KLF 5是KLF家族转录因子的成员，在许多胃肠道组织的增殖、分化和癌变中起关键作用。KLF 4在分化的上皮细胞中表达，而KLF 5在胃肠道（包括食管）的增殖细胞中发现。KLF 4调节许多对食管上皮分化至关重要的基因，并且在食管鳞状细胞癌中观察到KLF 4表达降低。尽管如此，KLF 4和KLF 5在食管肿瘤进展中的作用尚不清楚。在这里，使用TE 2细胞稳定感染逆转录病毒载体表达KLF 4或KLF 5，我们证明，KLF 4和KLF 5是关键的球员在一些细胞过程中的食管癌的发生至关重要。来自低分化食管鳞状细胞癌患者的TE 2细胞通常缺乏KLF 4和KLF 5。KLF 5在TE 2细胞中的表达抑制增殖，并且KLF 4和KLF 5在用过氧化氢处理后均降低活力并增加失巢凋亡。响应于UV照射的DNA损伤，KLF 5感染细胞的存活率降低，但KLF 4感染细胞的存活率不降低。KLF 4和KLF 5均上调紫外线照射后cdk抑制剂p21（waf 1/cip 1），但促凋亡蛋白BAX仅由KLF 5显著诱导。因此，KLF 4可能优先激活DNA修复途径，而KLF 5诱导UV照射后的DNA修复和凋亡。KLF 4或KLF 5在TE 2细胞中的表达也抑制侵袭，这与各自在预防肿瘤转移中的作用一致。总之，KLF 4和KLF 5通过影响增殖、凋亡和侵袭来调节食管癌的发生。
KLF4 and KLF5, members of the KLF family of transcription factors, play key roles in proliferation, differentiation, and carcinogenesis in a number of gastrointestinal tissues. While KLF4 is expressed in differentiating epithelial cells, KLF5 is found in proliferating cells of the gastrointestinal tract, including the esophagus. KLF4 regulates a number of genes vital for esophageal epithelial differentiation, and decreased expression of KLF4 is seen in esophageal squamous cancers. Nonetheless, the roles of KLF4 and KLF5 in esophageal tumor progression are not known. Here, using TE2 cells stably infected with retroviral vectors to express KLF4 or KLF5, we demonstrate that KLF4 and KLF5 are key players in a number of cellular processes critical for esophageal carcinogenesis. TE2 cells, derived from a patient with poorly differentiated esophageal squamous cancer, normally lack KLF4 and KLF5. Expression of KLF5 in TE2 cells inhibits proliferation, and both KLF4 and KLF5 decrease viability after treatment with hydrogen peroxide and increase anoikis. In response to DNA damage from UV irradiation, viability is decreased in KLF5 but not KLF4 infected cells. Both KLF4 and KLF5 upregulate the cdk inhibitor p21(waf1/cip1) following UV irradiation, but the pro-apoptotic protein BAX is markedly induced only by KLF5. Thus KLF4 may preferentially activate DNA repair pathways while KLF5 induces both DNA repair and apoptosis after UV irradiation. Expression of KLF4 or KLF5 in TE2 cells also inhibits invasion, consistent with a role for each in preventing tumor metastasis. In summary, KLF4 and KLF5 regulate esophageal carcinogenesis by affecting proliferation, apoptosis, and invasion.