Unit of Biochemistry, Department of Zoology, University of Madras, Chennai, India.
Clin Chim Acta. 2010 Dec 14;411(23-24):2067-72. doi: 10.1016/j.cca.2010.09.003. Epub 2010 Sep 8.
The molecular events that underlie the conversion of normal human gastric epithelium into adenocarcinoma are poorly understood. MUC1 overexpression and localization in mitochondria might confer cancer cells with attenuation of stress induced apoptosis. We studied MUC1 expression pattern, interaction with HSP70 and localization in mitochondria in preneoplastic and neoplastic human gastric tissues.
Immunohistochemistry and Western blot were used to study MUC1 expression pattern and localization in mitochondria. Coimmunoprecipitation was used to study MUC1 interaction with HSP70. MUC1 expression was correlated with other causative features including erbB2 expression.
MUC1 was expressed in 75.8% (147/194). MUC1 overexpression was detected in 50.0% (19/38 cases) dysplasia and 58.2% (32/55 cases) adenocarcinoma tissues. MUC1-CT-HSP70 interaction was seen in 71.66% (43/60 cases) and MUC1 localized to mitochondria in 33.33% (5/15) dysplasia samples and in 47.05% (8/17) adenocarcinoma samples. MUC1 expression showed significant association with smoking (χ(2)=5.945; p<0.015), alcohol consumption (χ(2)=4.055; p<0.044) and erbB2 positivity (χ(2)=10.75; p<0.001). MUC1 expression did not show appreciable association with age (χ(2)=0.15; p<0.698), sex (χ(2)=0.22; p<0.640) or Helicobacter pylori infection (χ(2)=3.06; p<0.080).
Significant correlation was found between MUC1 expression and smoking, alcohol and erbB2 expression. MUC1 showed aberrant expression in dysplasia and adenocarcinoma stages. MUC1 cytosolic tail was bound by HSP70 in all the stages but MUC1-CT was found to localize in mitochondria only in dysplasia and adenocarcinoma. MUC1-CT localization to mitochondria in dysplasia and adenocarcinoma might aid in the attenuation of epithelial stress response induced loss of polarity.
正常胃上皮细胞向腺癌转化的分子事件知之甚少。MUC1 的过度表达和在线粒体中的定位可能使癌细胞对应激诱导的细胞凋亡产生衰减。我们研究了癌前和肿瘤性人类胃组织中 MUC1 的表达模式、与 HSP70 的相互作用和在线粒体中的定位。
免疫组织化学和 Western blot 用于研究 MUC1 的表达模式和在线粒体中的定位。共免疫沉淀用于研究 MUC1 与 HSP70 的相互作用。MUC1 的表达与其他致病特征（包括 erbB2 表达）相关。
MUC1 在 75.8%（147/194）的病例中表达。在 50.0%（19/38 例）发育不良和 58.2%（32/55 例）腺癌组织中检测到 MUC1 的过度表达。在 71.66%（43/60 例）和 33.33%（5/15 例）发育不良样本和 47.05%（8/17 例）腺癌样本中均观察到 MUC1-CT-HSP70 相互作用，MUC1 定位于线粒体。MUC1 的表达与吸烟（χ(2)=5.945；p<0.015）、饮酒（χ(2)=4.055；p<0.044）和 erbB2 阳性（χ(2)=10.75；p<0.001）显著相关。MUC1 的表达与年龄（χ(2)=0.15；p<0.698）、性别（χ(2)=0.22；p<0.640）或幽门螺杆菌感染（χ(2)=3.06；p<0.080）无明显相关性。
MUC1 的表达与吸烟、饮酒和 erbB2 表达之间存在显著相关性。MUC1 在发育不良和腺癌阶段表现出异常表达。MUC1 胞质尾在所有阶段均与 HSP70 结合，但仅在发育不良和腺癌中发现 MUC1-CT 定位于线粒体。MUC1-CT 在发育不良和腺癌中的线粒体定位可能有助于减弱上皮应激反应诱导的极性丧失。
