Alterations in the p53-SOCS2 axis contribute to tumor growth in colon cancer
| Autor: | Baik-Hwan Cho, Mi-Jin Lee, Kyu-Yun Jang, Jong-Hwan Kim, Goung-Ran Yu, Dae-Ghon Kim, Sang Wook Kim, Hee-Chul Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Clinical Biochemistry lcsh:Medicine Suppressor of Cytokine Signaling Proteins Biochemistry Article Transcriptome lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cell Line Tumor medicine otorhinolaryngologic diseases Animals Humans lcsh:QD415-436 Molecular Biology Regulation of gene expression Gene knockdown Cell growth Chemistry Azoxymethane Gene Expression Profiling lcsh:R High-Throughput Nucleotide Sequencing Transfection Immunohistochemistry Gene Expression Regulation Neoplastic 030104 developmental biology Cytokine Cell Transformation Neoplastic Cell culture 030220 oncology & carcinogenesis Gene Knockdown Techniques Colonic Neoplasms Cancer research Molecular Medicine Female Tumor Suppressor Protein p53 |
| Zdroj: | Experimental and Molecular Medicine, Vol 50, Iss 4, Pp 1-10 (2018) Experimental & Molecular Medicine |
| ISSN: | 2092-6413 |
| Popis: | Altered expression of suppressor of cytokine signaling (SOCS) is found in various tumors. However, regulation of SOCS2 by upstream molecules has yet to be clearly elucidated, particularly in tumor cells. SCOCS2 expression was examined in tumor cells transfected with an inducible p53 expression system. The impact of SOCS2 on cell proliferation was measured with in vitro assays. Inhibition of tumorigenicity by SOCS2 knockdown was assessed via a mouse model. Expression profiles were compared and genes differentially expressed were identified using four types of p53-null cells (Saos, HLK3, PC3, and H1299) and the same cells stably expressing p53. Twelve kinds of target genes were simultaneously upregulated or downregulated by p53 in three or more sets of p53-null cells. SOCS2 expression was reciprocally inhibited by inducible p53 expression in p53-null cells, even colon cancer cells. SOCS2 promoter activity was inhibited by wild type but not mutant p53. SOCS2 knockdown inhibited tumor growth in vitro and in an animal xenograph model. SOCS2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. SOCS2 expression was heterogeneously upregulated in some human colon cancers. Thus, SOCS2 was upregulated by p53 dysfunction and seemed to be associated with the tumorigenic potential of colon cancer. Colon cancer: A delicate balance to regulate growth Insights into a signaling protein’s role in cell growth could inform new therapeutic strategies for treating colon cancer. SOCS-2 acts as an ‘off switch’ for cell signaling pathways. It has been identified as possibly protective against many cancers, although some cancers are associated with elevated SOCS-2 levels. Researchers led by Daeghon Kim at Chonbuk National University Hospital in South Korea have now shown that the effects of SOCS-2 are apparently dependent on how much of it is present. Moderate levels of SOCS-2 can suppress growth in colon cancer cells, but Kim’s team showed that excessive SOCS-2 has the opposite effect, promoting proliferation. The researchers also identified a gene commonly mutated in cancer cells that can drive overproduction of SOCS-2. Drugs that inhibit SOCS-2 or block its production may therefore offer useful treatments for colorectal cancer. |
| Databáze: | OpenAIRE |
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