MUC1 expression and its association with other aetiological factors and localization to mitochondria in preneoplastic and neoplastic gastric tissues.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Benjamin
J B Elisha
JB
Unit of Biochemistry, Department of Zoology, University of Madras, Chennai, India.
Jayanthi
Venkatraman
V
Devaraj
Halagowder
H
D000367:Age Factors; D000428:Alcohol Drinking / Q000378:metabolism; D017209:Apoptosis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism*; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D021381:Protein Transport; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012737:Sex Factors; D012907:Smoking / Q000378:metabolism; D013270:Stomach / Q000382:microbiology / Q000473:pathology*; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D018840:HSP70 Heat-Shock Proteins; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C060192:MUC1 protein, human; C508053:ERBB2 protein, human