LMP2/b1i as a potential biomarker of human uterine mesenchymal tumors under the combination of candidate molecules, cyclin E and calponin h1

Abstract

Uterine leiomyosarcoma (Ut-LMS) develops more often in myometrium of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of Ut-LMS is not substantially correlated with hormonal conditions, and the risk factor(s) are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant tumor Ut-LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to examine risk factor(s) associated with Ut-LMS, to establish a diagnosis and a clinical treatment method. The mice with a homozygous deficiency for proteasome b-ring subunit, low-molecular mass polypeptide (LMP)2/b1i spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. In the recent study, we found LMP2/b1i expression to be absent in human Ut-LMS, but present in other human uterine mesenchymal tumors including uterine LMA. Moreover, LMP2/b1i is reported to negatively regulate human Ut-LMS tumorigenesis. Additional experiments furthermore indicate the differential expressions of cyclin E and calponin h1 during human uterine mesenchymal tumors. Therefore, LMP2/b1i is a potential diagnostic biomarker under the combination of candidate molecules, cyclin E and calponin h1 for human Ut-LMS, and may be a targeted-molecule for a new therapeutic approach.