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Human trypsinogen in colorectal cancer
S J Williams1, D C Gotley, T M Antalis
1Cancer Metastasis Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
International Journal of Cancer
|June 8, 2001
Summary
Trypsinogen (TRY) isoforms were studied in colorectal cancer. TRY2 is common in colon tissue, but TRY1 up-regulation may indicate a metastatic phenotype in colon tumors.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Trypsinogen (TRY) is a pancreatic precursor to trypsin, crucial for digestive proteolysis.
- An isoform, TRY2, was identified as up-regulated in human colorectal cancers compared to normal colonic mucosa.
Purpose of the Study:
- To investigate the expression of TRY isoforms (TRY1 and TRY2) in colorectal tumors.
- To determine the association of TRY isoform expression with colorectal cancer progression and metastatic potential.
Main Methods:
- Differential display of cDNAs from human colorectal tumors and normal mucosa.
- Northern blot analysis to quantify TRY transcript levels.
- Semi-quantitative multiplex RT-PCR to evaluate TRY1 and TRY2 mRNA expression.
- Immunostaining for TRY protein expression in tissue specimens.
Main Results:
- TRY transcripts were up-regulated in 29% of colon tumors.
- TRY mRNA was detected in all 6 colorectal cancer cell lines, with higher levels in metastatic lines.
- TRY2 mRNA was more common than TRY1 mRNA in normal and tumor tissues.
- TRY1 mRNA expression was specific to metastatic tumor lines, suggesting its association with metastasis.
Conclusions:
- TRY2 is the predominant trypsinogen isoform in colon tissue.
- Up-regulation of TRY1 expression in colon tumors may be linked to a metastatic phenotype.
- Differential expression of TRY isoforms could serve as a biomarker for colorectal cancer metastasis.