Volume : IV, Issue : IX, September - 2015

Sarcomagenesis in Psmb9-deficient mice; involvement of defective IRF1 activation.

Takuma Hayashi

Abstract :

Uterine leiomyosarcoma (Ut-LMS) is a highly metastatic smooth muscle neoplasm for which CALPONIN h1 is suspected to play a biological role as a tumor suppressor. We previously reported that proteasome β-subunit (Psmb)9-deficient mice spontaneously developed Ut-LMS through malignant transformation of the myometrium, which implicated this protein as an anti-oncogenic candidate. We also suggested that PSMB9 may negatively regulate Ut-LMS independently of its role in the proteasome. Interferon regulatory factor (IRF)1 was the first member of the IRF family to be identified. Initially described as a transcription factor that was able to activate the expression of Interferon (IFN)-γ responsible genes, Irf-1 has been shown to play roles in the immune response, regulation of apoptosis, and tumor suppression. The aim of this study was to elucidate the molecular mechanism of sarcomagenesis using the samples of Ut-LMSs from Psmb9-deficient mice and tissue sections of human Ut-LMSs and normal myometrium from patients. The expressions of the IFN-γ signal molecules, IRF1, IRF2, STAT1, PSMB5/β5i, PSMB9/β1i, PSMB8/β3i, PSMB10/β2i and β-ACTIN were examined with the tissue samples of mouse and human clinical materials. Physiological significant of IRF1 in sarcomagenesis was demonstrated by xenograft studies. In the present study, several lines of evidence indicated that although treatments with IFN-γ strongly induced the activation of STAT1 as a transcriptional activator, its target molecule, IRF1, was not clearly produced in Psmb9-deficient uterine smooth muscle cells (Ut-SMCs). Defective IRF1 expression may result in the malignant transformation of Ut-SMCs. The modulation of PSMB9 may lead to new therapeutic approaches in human Ut-LMS. (251 words)

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Article: Download PDF    DOI : https://www.doi.org/10.36106/gjra  

Cite This Article:

Takuma Hayashi Sarcomagenesis in Psmb9-deficient mice; involvement of defective IRF1 activation. Global Journal For Research Analysis, Vol: 4, Issue: 9 September 2015

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