Open AccessInhibition of α‐mannosidase Man2c1 gene expression suppresses growth of esophageal carcinoma cells through mitotic arrest and apoptosis
Author(s) -
Tian Yun,
Ju Ji Yu,
Zhou Yi Qun,
Liu Yin,
Zhu Li Ping
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01019.x
Subject(s) - mitosis , apoptosis , microbiology and biotechnology , biology , telophase , cell cycle , microtubule , cell cycle checkpoint , transfection , small interfering rna , cancer research , cell culture , anaphase , genetics
To study the effects of suppressed α‐mannosidase Man2c1 gene expression on EC9706 human esophageal carcinoma cells, the cells were treated with short interfering RNA. Growth inhibition of EC9706 cells was observed when Man2c1 expression was inhibited in this way. Flow cytometric analysis showed accumulation of cells in S and G 2 –M phases, as well as cell apoptosis. The mitotic index test showed cell‐cycle arrest at the M checkpoint. Although the percentage of cells in (pro)metaphase increased, the proportion of cells in anaphase and telophase decreased. Apoptosis was trigged by mitotic arrest. Furthermore, microtubules in EC9607 cells were examined by means of fluorescence staining of α‐tubulin. Although control cells showed a nest‐like microtubule network, the microtubule network in experimental cells was vague and condensed at the perinuclear region. Some cells with Man2c1 suppression had large protrusions of cytoplasm, some of which linked with the main body through a long, thin connection. Western blotting showed that tubulin polymerization was inhibited. The data imply that induction of mitotic arrest and consequent apoptosis resulted from microtubule disorganization, which appears to be one of the major cellular mechanisms by which suppressed expression of the Man2c1 gene causes growth inhibition of EC9706 esophageal carcinoma cells. In addition, Man2c1 suppression results in upregulation of E‐cadherin, α‐catenin, and β‐catenin expression in cells. ( Cancer Sci 2008; 99: 2428–2434)