Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer.
BACKGROUND
Cysteine proteases like cathepsins are widely distributed proteolytic enzymes and form tight equimolar complexes with cystatins at their active sites. Among cystatins, CST1, encoding cystatin SN, is a member of the type 2 salivary cystatin family found in a variety of fluids and secretions, including plasma, tears, and saliva. CST1 was identified as an upregulated gene in gastric cancer tissues compared to noncancerous regions using our Affymetrix GeneChip microarray.


METHODS
The upregulation of CST1 in gastric cancer was analyzed using RT-PCR (n=15), immnohistochemistry, and clinicopathological (n=77) analysis. CST1-siRNA was used for the suppression of CST1 gene expression and cathepsin proteolytic activity was assayed.


RESULTS
CST1 was upregulated in cancerous lesions of gastric cancer tissues compared to noncancerous regions and clinicopathological analysis showed a significant correlation between high expression of CST1 and pTNM stage (p=0.044). In CST1-siRNA transfected cells, cell proliferation was reduced and the proteolytic activity of cathepsins was increased.


CONCLUSIONS
CST1 might be highly involved in gastric tumorigenesis and regulate the proteolytic activity of cysteine proteases.
Choi
Eun Hwa
EH
Medical Genomic Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Kim
Jong-Tae
JT
Kim
Joo Heon
JH
Kim
Soo-Young
SY
Song
Eun Young
EY
Kim
Jae Wha
JW
Kim
Seon-Young
SY
Yeom
Young Il
YI
Kim
Ik-Hwan
IH
Lee
Hee Gu
HG
D002403:Cathepsins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055333:Salivary Cystatins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D055333:Salivary Cystatins; D002403:Cathepsins; D018021:Lithium Chloride