Molecular mechanisms of uterine leiomyosarcomas: Involvement of defect in LMP2 expression

Takuma Hayashi, Yuto Shimamura, Taro Saegusa, Akiko Horiuchi, Yukihiro Kobayashi, Nobuyoshi Hiraoka, Yae Kanai, Hiroyuki Aburatani, Kenji Sano, Ikuo Konishi

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Patients with uterine leiomyosarcoma (LMS) typically present with vaginal bleeding, pain, and a pelvic mass. Typical presentations with hypercalcemia or eosinophilia have been reported. Radiographic evaluation with combined positron emission tomography/computed tomography may assist in the diagnosis and surveillance of women with uterine LMS. A recently developed risk-assessment index is highly predictive of disease-specific survival. Ovarian preservation does not appear to negatively impact outcome, and the addition of adjuvant therapy after surgical treatment does not seem to improve survival. It is noteworthy that LMP2-deficient mice exhibit spontaneous development of uterine LMS with a disease prevalence of ∼37% by 12 months of age. The LMP2 gene is transcribed from a promoter containing an interferon (IFN-γ-response factor element; thus, the IFN-γ-signal strongly induces LAP2 expression. Furthermore, a recent report demonstrated the loss of ability to induce LMP2 expression, which is an interferon IFN-γ-inducible factor, in human uterine LMS tissues and cell lines. Analysis of human uterine LMS shows somatic mutations in the IFN-γ signalling pathway, thus the loss of LMP2 induction is attributable to a defect in the earliest steps of the IFN-γ signalling pathway. The discovery of an impaired key cell-signalling pathway may provide new targets for diagnostic approaches and therapeutic intervention.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalGene Regulation and Systems Biology
Volume2008
Issue number2
DOIs
Publication statusPublished - 2008 Jul 22

Keywords

  • IFN-γ signalling pathway
  • Leiomyosarcoma
  • Uterus
  • lmp2

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Computer Science Applications

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  • Cite this

    Hayashi, T., Shimamura, Y., Saegusa, T., Horiuchi, A., Kobayashi, Y., Hiraoka, N., Kanai, Y., Aburatani, H., Sano, K., & Konishi, I. (2008). Molecular mechanisms of uterine leiomyosarcomas: Involvement of defect in LMP2 expression. Gene Regulation and Systems Biology, 2008(2), 297-305. https://doi.org/10.4137/grsb.s470