Proteasomes in Patient Rectal Cancer and Different Intestine Locations: Where Does Proteasome Pool Change?

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Rectal cancer surgery requires precise tumor removal, including margins.
• Identifying tumor-specific molecular changes is crucial for determining safe resection lengths.
• Proteasomes, key protein hydrolysis enzymes, play roles in cellular processes and disease.

Purpose of the Study:

• To investigate proteasome functioning in rectal adenocarcinoma and adjacent/distant tissues.
• To analyze chymotrypsin-like and caspase-like proteasome activities and their spatial distribution.
• To assess the expression of proteasome subunits and activators in relation to tumor presence.

Main Methods:

• Analysis of chymotrypsin-like and caspase-like proteasome activities using specific substrates (Suc-LLVY-AMC and Z-LLE-AMC).
• Quantification of immune subunits (LMP2, LMP7) and activators (19S, PA28αβ) expression.
• Native electrophoresis to characterize proteasome subtypes in tumor tissue.

Main Results:

• Proteasome activities decreased in the order: cancer > adjacent tissue > proximal and distal tissues.
• No significant difference in proteasome activity was observed between proximal and distal tissues.
• Proteasome subtype containing LMP2 and PA28αβ showed the most significant changes in tumor tissue.
• Distal fragments (2-4 cm from tumor) showed no notable changes in the proteasome pool.

Conclusions:

• Proteasome activity and composition are significantly altered in rectal cancer and adjacent tissues.
• The LMP2-PA28αβ proteasome subtype is important in rectal adenocarcinoma.
• Distal rectal fragments up to 4 cm from the tumor maintain normal proteasome functioning, suggesting suitability for resection margins.