Changes in proteasome pool in human papillary thyroid carcinoma development

Шарова, Н. П.; Astakhova, T. Yu.; Karpova, Yaroslava; Lyupina, Yu. V.; Alekhin, Alexander I.; Goncharov, Nikolai G.; Сумеди, И. Р.; Cherner, Vyacheslav A.; Родоман, Г. В.; Kuznetsov, Nikolay V.; Erokhov, Pavel A.

doi:10.2478/s11535-011-0040-x

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…It was in tumor cells (not stroma cells) that the main amounts of subunit LMP2 and activator PA700 were fixed by method of immunohistochemistry. Relationships like these were earlier detected for thyroid cancer [32] . Perhaps, immune subunit LMP2 performs anti-stress functions in cells of these tumors and promotes their survival.…”

Section: Discussionsupporting

confidence: 67%

Proteasome Functioning in Breast Cancer: Connection with Clinical-Pathological Factors

et al. 2014

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Breast cancer is one of four oncology diseases that are most widespread in the world. Moreover, breast cancer is one of leading causes of cancer-related deaths in female population within economically developed regions of the world. So far, detection of new mechanisms of breast cancer development is very important for discovery of novel areas in which therapy approaches may be elaborated. The objective of the present study is to investigate involvement of proteasomes, which cleave up to 90% of cellular proteins and regulate numerous cellular processes, in mechanisms of breast cancer development. Proteasome characteristics in 106 patient breast carcinomas and adjacent tissues, as well as relationships of detected proteasome parameters with clinical-pathological factors, were investigated. Proteasome chymotrypsin-like activity was evaluated by hydrolysis of fluorogenic peptide Suc-LLVY-AMC. The expression of proteasome subunits was studied by Western-blotting and immunohistochemistry. The wide range of chymotrypsin-like activity in tumors was detected. Activity in tumors was higher if compared to adjacent tissues in 76 from 106 patients. Multiple analysis of generalized linear models discovered that in estrogen α-receptor absence, tumor growth was connected with the enhanced expression of proteasome immune subunit LMP2 and proteasome activator PA700 in tumor (at 95% confidence interval). Besides, by this analysis we detected some phenomena in adjacent tissue, which are important for tumor growth and progression of lymph node metastasis in estrogen α-receptor absence. These phenomena are related to the enhanced expression of activator PA700 and immune subunit LMP7. Thus, breast cancer development is connected with functioning of immune proteasome forms and activator PA700 in patients without estrogen α-receptors in tumor cells. These results could indicate a field for search of new therapy approaches for this category of patients, which has the worst prognosis of health recovery.

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Section: Discussionsupporting

confidence: 67%

Proteasome Functioning in Breast Cancer: Connection with Clinical-Pathological Factors

et al. 2014

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Rubio

Bencomo‐Alvarez

Young

et al. 2021

Cells

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Ever since the ubiquitin proteasome system was characterized, efforts have been made to manipulate its function to abrogate the progression of cancer. As a result, the anti-cancer drugs bortezomib, carfilzomib, and ixazomib targeting the 26S proteasome were developed to treat multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, among others. Despite success, adverse side effects and drug resistance are prominent, raising the need for alternative therapeutic options. We recently demonstrated that knockdown of the 19S regulatory components, 26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3), resulted in increased apoptosis of chronic myeloid leukemia (CML) cells, but had no effect on normal controls, suggesting they may be good targets for therapy. Therefore, we hypothesized that PSMD1 and PSMD3 are potential targets for anti-cancer therapeutics and that their relevance stretches beyond CML to other types of cancers. In the present study, we analyzed PSMD1 and PSMD3 mRNA and protein expression in cancerous tissue versus normal controls using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), comparing expression with overall survival. Altogether, our data suggest that PSMD1 and PSMD3 may be novel putative targets for cancer prognosis and therapy that are worthy of future investigation.

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“…It is intriguing that in other tumor types (patient thyroid papillary carcinoma, mouse hepatocellular carcinoma and mammary gland cancer) as well as in patient rectal cancer the increase in LMP2 subunit expression is much more significant in comparison with the expression of LMP7 subunit [ 2 , 21 , 22 ]. It indicates the universal role of the proteasomes with LMP2 subunit in the tumor development.…”

Section: Resultsmentioning

confidence: 99%

“…Solving this issue is tightly related to the detection of intestine areas where there are no changes in the molecule functioning that are intrinsic for tumor. In this regard, we paid attention to proteasomes, the main actors in protein hydrolysis, which largely determine the tumor fate [ 1 , 2 , 3 , 4 ]. Proteasomes control cellular proteome and regulate different processes by protein degradation and production of biologically active polypeptides and peptides.…”

Section: Introductionmentioning

confidence: 99%

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

Erokhov

Куликов

Karpova

et al. 2021

Cancers

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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.

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Changes in proteasome pool in human papillary thyroid carcinoma development

Cited by 8 publications

References 36 publications

Proteasome Functioning in Breast Cancer: Connection with Clinical-Pathological Factors

Proteasome Functioning in Breast Cancer: Connection with Clinical-Pathological Factors

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

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

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