Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma

Takuma Hayashi, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Mari Kasai, Tomoyuki Ichimura, Satoru Nagase, Osamu Ishiko, Tanri Shiozawa, Yae Kanai, Nobuo Yaegashi, Hiroyuki Aburatani, Susumu Tonegawa, Ikuo Konishi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma 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 leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. Aims: It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic-biomarker and a clinical treatment method. Patients and Methods: Histology and Immunofluorescence Staining: Uteri obtained from LMP2-/- mice or its parental mice (C57BL/6 mice) were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections (5 μm) were prepared and stained with H&E for routine histological examination or were processed further for immunofluorescence staining with appropriate antidodies. Furthermore, a total of 101 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results: Homozygous deficient mice for a proteasome β1i subunit, LMP2 spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine leiomyosarcoma was demonstrated, but present in human leiomyoma and myometrium. Conclusions: Loss in LMP2 expression may be one of the risk factors for human uterine leiomyosarcoma. LMP2 may be a potential diagnostic-biomarker and targeted-molecule for a new therapeutic approach.

Original languageEnglish
Pages (from-to)394-399
Number of pages6
JournalNorth American Journal of Medical Sciences
Volume3
Issue number9
DOIs
Publication statusPublished - 2011 Sep
Externally publishedYes

Fingerprint

Leiomyosarcoma
Leiomyoma
Uterus
Myometrium
Biomarkers
Staining and Labeling
Fluorescent Antibody Technique
Muscle Neoplasms
Smooth Muscle Tumor
LMP-2 protein
Human Development
Inbred C57BL Mouse
Paraffin
Formaldehyde
Smooth Muscle
Neoplasms
Histology
Immunohistochemistry
Hormones
Neoplasm Metastasis

Keywords

  • Diagnostic-biomarker
  • LMP2
  • Uterine leiomyoma
  • Uterine leiomyosarcoma

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hayashi, T., Horiuchi, A., Sano, K., Hiraoka, N., Kasai, M., Ichimura, T., ... Konishi, I. (2011). Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma. North American Journal of Medical Sciences, 3(9), 394-399. https://doi.org/10.4297/najms.2011.3394

Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma. / Hayashi, Takuma; Horiuchi, Akiko; Sano, Kenji; Hiraoka, Nobuyoshi; Kasai, Mari; Ichimura, Tomoyuki; Nagase, Satoru; Ishiko, Osamu; Shiozawa, Tanri; Kanai, Yae; Yaegashi, Nobuo; Aburatani, Hiroyuki; Tonegawa, Susumu; Konishi, Ikuo.

In: North American Journal of Medical Sciences, Vol. 3, No. 9, 09.2011, p. 394-399.

Research output: Contribution to journalArticle

Hayashi, T, Horiuchi, A, Sano, K, Hiraoka, N, Kasai, M, Ichimura, T, Nagase, S, Ishiko, O, Shiozawa, T, Kanai, Y, Yaegashi, N, Aburatani, H, Tonegawa, S & Konishi, I 2011, 'Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma', North American Journal of Medical Sciences, vol. 3, no. 9, pp. 394-399. https://doi.org/10.4297/najms.2011.3394
Hayashi, Takuma ; Horiuchi, Akiko ; Sano, Kenji ; Hiraoka, Nobuyoshi ; Kasai, Mari ; Ichimura, Tomoyuki ; Nagase, Satoru ; Ishiko, Osamu ; Shiozawa, Tanri ; Kanai, Yae ; Yaegashi, Nobuo ; Aburatani, Hiroyuki ; Tonegawa, Susumu ; Konishi, Ikuo. / Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma. In: North American Journal of Medical Sciences. 2011 ; Vol. 3, No. 9. pp. 394-399.
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abstract = "Background: Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma 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 leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. Aims: It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic-biomarker and a clinical treatment method. Patients and Methods: Histology and Immunofluorescence Staining: Uteri obtained from LMP2-/- mice or its parental mice (C57BL/6 mice) were fixed in 10{\%} buffered formalin, incubated in 4{\%} paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections (5 μm) were prepared and stained with H&E for routine histological examination or were processed further for immunofluorescence staining with appropriate antidodies. Furthermore, a total of 101 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results: Homozygous deficient mice for a proteasome β1i subunit, LMP2 spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40{\%} by 14 months of age. Defective LMP2 expression in human uterine leiomyosarcoma was demonstrated, but present in human leiomyoma and myometrium. Conclusions: Loss in LMP2 expression may be one of the risk factors for human uterine leiomyosarcoma. LMP2 may be a potential diagnostic-biomarker and targeted-molecule for a new therapeutic approach.",
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AU - Horiuchi, Akiko

AU - Sano, Kenji

AU - Hiraoka, Nobuyoshi

AU - Kasai, Mari

AU - Ichimura, Tomoyuki

AU - Nagase, Satoru

AU - Ishiko, Osamu

AU - Shiozawa, Tanri

AU - Kanai, Yae

AU - Yaegashi, Nobuo

AU - Aburatani, Hiroyuki

AU - Tonegawa, Susumu

AU - Konishi, Ikuo

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