Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer.

Abstract

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.

• Authors: Eun Hwa Choi, Jong-Tae Kim, Joo Heon Kim, Soo-Young Kim, Eun Young Song, Jae Wha Kim, Seon-Young Kim, Young Il Yeom, Ik-Hwan Kim, Hee Gu Lee
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 406 Issue 1-2 Pg. 45-51 (Aug 2009) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 19463800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Salivary Cystatins
• Cathepsins
• Lithium Chloride

Topics

• Cathepsins (antagonists & inhibitors)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cysteine Proteinase Inhibitors (genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Immunohistochemistry
• Lithium Chloride (pharmacology)
• Male
• Reverse Transcriptase Polymerase Chain Reaction
• Salivary Cystatins (genetics)
• Stomach Neoplasms (enzymology, genetics, metabolism, pathology)
• Up-Regulation (drug effects)