Review Article
Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma
Takuma Hayashi1,10,
Akiko Horiuchi2, Kenji Sano3, Nobuyoshi Hiraoka4,
Mari Kasai5, Tomoyuki Ichimura5
Satoru Nagase6, Osamu Ishiko5, Tanri Shiozawa2,
Yae Kanai4, Nobuo Yaegashi6
Hiroyuki Aburatani7, Susumu Tonegawa8, Ikuo Konishi9
1Department
of Immunology and Infectious Disease, Shinshu University Graduate School of
Medicine, Japan.
2Department
of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan.
3Department
of Laboratory Medicine, Shinshu University Hospital, Japan.
4Pathology
Division, National Cancer Center Research Institute, Japan.
5Department
of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine,
Japan.
6Department
of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine,
Japan.
7The
Cancer System Laboratory, Research Center for Advanced Science and Technology,
The University of Tokyo, Japan.
8Picower
Institution and Department of Biology,
Massachusetts Institute of Technology, USA.
9Department
of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine,
Japan.
10Promoting
Business using Advanced Technology, Japan Science and Technology Agency, Japan.
Citation:
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.
Involvement of proteasome β1i subunit,
LMP2, on development of uterin leiomyosarcma.
North Am
J Med Sci
2011; 3: 394-399.
doi:
10.4297/najms.2011.3394
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.
Keywords:
LMP2, uterine leiomyosarcoma, uterine leiomyoma, diagnostic-biomarker
Correspondence to:
Takuma Hayashi, Department of Immunology and Infectious Disease, Shinshu
University Graduate School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano
390-8621, Japan. Email:
ryukun0204@yahoo.co.jp