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

Abstract

A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations. Chymotrypsin-like and caspase-like activities, open to complex influence of different factors, were analyzed in 43–54 samples by Suc-LLVY-AMC- and Z-LLE-AMC-hydrolysis correspondingly. Both activities may be arranged by the decrease in the location row: cancer→adjacent tissue→proximal (8–20 cm from tumor) and distal (2 and 4 cm from tumor) sides. These activities did not differ noticeably in proximal and distal locations. Similar patterns were detected for the activities and expression of immune subunits LMP2 and LMP7 and expression of 19S and PA28αβ activators. The largest changes in tumor were related to proteasome subtype containing LMP2 and PA28αβ that was demonstrated by native electrophoresis. Thus, the results indicate a significance of subtype LMP2-PA28αβ for tumor and absence of changes in proteasome pool in distal fragments of 2–4 cm from tumor.

26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy

“…Since the UPS is composed of a series of highly regulated proteins, there is ample opportunity to discover new targets for cancer therapy. Indeed, the expression of many different proteasome subunits are reported to be altered in multiple different cancers, including human papillary thyroid carcinoma [ 18 ], breast cancer [ 19 , 20 , 21 , 22 , 23 ], colon cancer [ 24 , 25 ], and ovarian cancer [ 26 ], among others [ 27 , 28 , 29 , 30 ]. We recently demonstrated that two members of the 19S regulatory complex, 26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3), may be potential targets for therapy in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) cells.…”