Involvement of proteasome b1i subunit, LMP2, on uterine leiomyosarcma tumorigenesis

Takuma Hayashi,Akiko Horiuchi,Ikuo Konishi

doi:10.1038/npre.2011.6478.1

Takuma Hayashi, Akiko Horiuchi + Show 1 more

Open Access

https://doi.org/10.1038/npre.2011.6478.1

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Journal: Nature Precedings	Publication Date: Sep 30, 2011
License type: CC BY 3.0

Affiliation: Shinshu University, Kyoto University

Abstract

AbstractAlthough the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine LMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with human uterine LMS, in order to establish a clinical treatment method. Homozygous deficient mice for a proteasome subunit b1i/LMP2 spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine LMS was demonstrated, but present in human LMA. Therefore, loss in LMP2 expression may be one of the risk factors for human uterine LMS. LMP2 may be a potential diagnostic-biomarker and targeted- molecule for a new therapeutic approach.

Highlights

The uterus, the organ in which the embryo grows, is composed of three layers, the uterine endometrium, myometrium and a serous membrane enveloping the uterus, the myometrium is composed of smooth muscle
The term uterine tumor refers to an epithelial malignant tumor of the uterus, which is roughly classified as a tumor of the uterine cervix or the uterine body
While most tumors of the uterine body are adenocarcinomas derived from the subintimal gland, tumors of the uterine cervix are classified into squamous cancer and adenocarcinoma

Summary

Introduction

The uterus, the organ in which the embryo grows, is composed of three layers, the uterine endometrium, myometrium and a serous membrane enveloping the uterus, the myometrium is composed of smooth muscle. Loss in LMP2 expression may be one of the risk factors for human uterine Development of malignant uterine tumor in LMP2-deficient mice: Cytoplasmic proteins are mostly degraded by a protease complex, which has many substrates consisting of twenty-eight 20 to 30-kDa subunits, referred to as the proteasome[8].

Results

Conclusion