Proteasome Subunit LMP2/β1i as a Biomarker for Human Uterine Mesenchymal Tumors
Journal Title: Journal of Oncobiomarkers - Year 2013, Vol 1, Issue 2
Abstract
The proteasomal degradation pathway is essential for many cellular processes, including the cell cycle, regulation of gene expression, and responses to oxidative stress. The proteasome most exclusively used in mammals is the cytosolic 26S proteasome, which has a molecular mass of approximately, 2000 kilodaltons (kDa) and contains one 20S protein subunit and two 19S regulatory cap subunits. The 20S particle is assembled from two half-proteasomes, each of which consists of a seven-membered pro-β-ring attached to a seven-membered α-ring. Component of β-ring, low-molecular mass polypeptide (LMP)2/β1ideficient mice spontaneously develop uterine leiomyosarcoma (Ut-LMS), with a disease prevalence of ~40% by 14 months of age. Recent studies on human and mouse uterine tissues revealed the defective expression of LMP2/β1i in human Ut-LMS, and this was attributed to the interferon (IFN)-γ pathway and the specific effects of Janus kinase (JAK)-1 somatic mutation on LMP2/β1i transcriptional activation. Furthermore, an analysis of a human Ut-LMS cell line clarified the biological significance of LMP2/β1i in malignant myometrium transformation and the cell cycle; thus, implicating LMP2/β1i as an anti-tumorigenic candidate. The development of gynecological tumors is often correlated with the secretion of female hormones; however, the development of Ut-LMS has not been correlated with hormonal conditions, and the risk factors remain unknown. Therefore, the defective expression of LMP2/β1i may be a risk factor for human Ut-LMS. LMP2/β1i is a potential diagnostic biomarker for Ut-LMS, and may be a targeted molecule for a new clinical therapeutic approach.
Authors and Affiliations
Takuma Hayashi
Keywords
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- EP ID EP206250
- DOI 10.13188/2325-2340.1000007
- Views 96
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