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患者直肠癌及不同肠道部位的蛋白酶体:蛋白酶体库在何处发生变化?

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

作者信息

Erokhov Pavel A, Kulikov Alexey M, Karpova Yaroslava D, Rodoman Grigory V, Sumedi Ilia R, Goncharov Artem L, Razbirin Dmitry V, Gorelova Vera S, Sharova Natalia P, Astakhova Tatiana M

机构信息

Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 26 Vavilov Street, 119334 Moscow, Russia.

Pirogov Russian National Research Medical University of Ministry of Health of Russian Federation, 1 Ostrovityanov Street, 117997 Moscow, Russia.

出版信息

Cancers (Basel). 2021 Mar 5;13(5):1108. doi: 10.3390/cancers13051108.

DOI:10.3390/cancers13051108
PMID:33807574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7961961/
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.

摘要

直肠癌手术中的一个特殊问题与需要连同肿瘤一起适当切除肠段有关,包括靠近括约肌的片段。为了确定要切除的片段长度,有必要揭示肿瘤特有的分子功能未发生变化的区域。本研究的目的是调查蛋白酶体(蛋白质水解的主要参与者)在直肠癌患者以及不同肠段位置的功能。分别通过Suc-LLVY-AMC和Z-LLE-AMC水解对43至54个样本分析了易受不同因素综合影响的胰凝乳蛋白酶样和半胱天冬酶样活性。这两种活性可能会按照位置顺序降低排列:癌症→相邻组织→近端(距肿瘤8 - 20厘米)和远端(距肿瘤2和4厘米)侧。这些活性在近端和远端位置没有明显差异。免疫亚基LMP2和LMP7的活性、表达以及19S和PA28αβ激活剂的表达也检测到类似模式。通过非变性电泳证明,肿瘤中最大的变化与含有LMP2和PA28αβ的蛋白酶体亚型有关。因此,结果表明LMP2 - PA28αβ亚型对肿瘤具有重要意义,并且在距肿瘤2 - 4厘米的远端片段中蛋白酶体库没有变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/bac876f94fe5/cancers-13-01108-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/c8412c98f7d2/cancers-13-01108-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/9f185909b837/cancers-13-01108-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/6cd928a6bb21/cancers-13-01108-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/45580e156a5e/cancers-13-01108-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/e35079362111/cancers-13-01108-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/bac876f94fe5/cancers-13-01108-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/c8412c98f7d2/cancers-13-01108-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/9f185909b837/cancers-13-01108-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/6cd928a6bb21/cancers-13-01108-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/45580e156a5e/cancers-13-01108-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/e35079362111/cancers-13-01108-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/7961961/bac876f94fe5/cancers-13-01108-g006.jpg

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