A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor

Takuma Hayashi; Akiko Horiuchi.; Nobuo Yaegashi.; Tanri Shiozawa.; Susumu Tonegawa.; Ikuo Konishi

doi:doi:10.11648/j.crj.20130101.11

| Peer-Reviewed

A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor

Takuma Hayashi, Akiko Horiuchi., Nobuo Yaegashi., Tanri Shiozawa., Susumu Tonegawa., Ikuo Konishi

Published in Cancer Research Journal (Volume 1, Issue 1)

Received: 8 April 2013 Published: 2 May 2013

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer 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 uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, to establish a treatment method. Proteasome LMP2/1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/1i expression to be absent in human LMS, but present in human LMA. Therefore, defec-tive-LMP2/1i expression may be one of the risk factors for LMS. LMP2/1i is a potential diagnostic-biomarker under the combination of candidate molecules for uterine mesenchymal tumors, especially uterine LMS, and may be a tar-geted-molecule for a new therapeutic approach. (160 words)

Published in	Cancer Research Journal (Volume 1, Issue 1)
DOI	10.11648/j.crj.20130101.11
Page(s)	1-6
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2013. Published by Science Publishing Group

Keywords

LMP2/β1i, Uterine Leiomyosarcoma, Uterine Leiomyoma, Biomarker

References

[1]	Zaloudek C, Hendrickson MR. Mesenchymal tumors of the uterus, in Kurman RJ.(ed): Blaustein`s Pathology of the Female Genital Tract (ed 5). New York, Springer-Verlag 2002; 5: 561-78.
[2]	Wu TI, Chang TC, Hsueh S, Hsu KH, Chou HH, Huang HJ, Lai CH. Prognostic factors and impact of adjuvant chemo-therapy for uterine leiomyosarcoma. Gynecol. Oncol. 2006; 100: 166-72.
[3]	Leitao MM, Soslow RA, Nonaka D, Olshen AB, Aghajanian C, Sabbatini P, Dupont J, Hensley M, Sonoda Y, Barakat RR, Anderson S. Tissue microarray immunohisto chemical ex-pression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma. Cancer 2004; 101: 1455-62.
[4]	Perez EA, Pusztai L, Van de Vijver M. Improving patient care through molecular diagnostics. Semin. Oncol. 2004; 31: 14-20.
[5]	http://www.cancer.gov/cancertopics/pdq/treatment/uterinesarcoma/HealthProfessional/page1#Section_87
[6]	http://cancer.gov/cancertopics/pdq/treatment/uterinesarcoma/HealthProfessional
[7]	Evans HL, Chawla SP, Simpson C, Finn KP. Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer 1988; 62: 2239-47.
[8]	Kurma RJ. Pathology of the Female Genital Tract, 4th ed. New York, Springer-Verlag; 2001; 4: 499.
[9]	Diagnostic Criteria for LMS, Adapted from 2003 WHO Guidelines: (2003) World Health Organization Classification of Tumours: Pathology and Genetics, Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, France.
[10]	Lin JF, Slomovitz BM. Uterine sarcoma. Curr. Oncol. Rep. 2008; 10: 512-8.
[11]	Amant F, Coosemans A, Debiec-Rychter M, Timmerman D, Vergote I. Clinical management of uterine sarcomas. Lancet Oncol. 2009; 10: 1188-98.
[12]	Miettinen M, Fetsch JF. Evaluation of biological potential of smooth muscle tumours. Histopathol. 2006; 48: 97-105.
[13]	Peters JM, Franke WW, Kleinschmidt JA. Distinct 19 S and 20 S subcomplexes of the 26 S proteasome and their distribution in the nucleus and the cytoplasm. J. Biol. Chem. 1994; 269: 7709–18.
[14]	Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. 2004 "3". Mol Cell Biol (5th ed.). New York: W.H. Freeman and CO. 2004; 5:66–72.
[15]	Konstantinova IM, Tsimokha AS, Mittenberg AG. Role of proteasomes in cellular regulation. Intl. Rev. Cell. Mol. Biol. 2008; 267: 59–124.
[16]	Wang J, Maldonado MA. The Ubiquitin-Proteasome System and Its Role in Inflammatory and Autoimmune Diseases. Cell. Mol. Immunol. 2006; 3: 255–61.
[17]	Muchamuel T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J, Shwonek P, Parlati F, Demo SD, Bennett MK, Kirk CJ, Groettrup M. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature Med. 2009; 15: 781-8.
[18]	Van Kaer L, Ashton-Rickardt PG, Eichelberger M, Gaczynska M, Nagashima K, Rock KL, Goldberg AL, Doherty PC, Tonegawa S. Altered peptidase and viral-specifi c T cell response in LMP2 mutant mice. Immunity 1994; 1: 533-41.
[19]	Hayashi T, Faustman DL. Development of spontaneous uterine tumors in low molecular mass polypeptide-2 knockout mice. Cancer Res. 2002; 62: 24-7.
[20]	Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shi-ozawa T, Tonegawa S, Konishi I. Molecular approach on uterine leiomyosarcoma: LMP2-deficient mice as an animal model of spontaneous uterine leiomyosarcoma. Sarcoma 2011: 476498. Epub 2011 Mar 8.
[21]	Hayashi T, Kobayashi Y, Kohsaka S, Sano K. mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-gamma inducibility of TAP1 and LMP2. Oncogene 2006; 25: 4016-26.
[22]	Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichi-mura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I. Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. Sci. Rep. 2011; 1:180\| DOI:10.1038/srep00180
[23]	Zhai YL, Kobayashi Y, Mori A, Orii A, Nikaido T, Konishi I, Fujii S. Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas. Intl. J. Gynecol. Pathol. 2004; 18: 20-8.
[24]	Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichi-mura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I. Potential role of LMP2 as an anti-oncogenic factor in human uterine lei-omyosarcoma: morphological significance of calponin h1. FEBS Letter 2012; 586: 1824-31.
[25]	Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Sudo T, Ishiko O, Yaegashi N, Aburatani H, Konishi I. Potential diagnostic biomarkers for human uterine mesenchymal tumors: Especially LMP2/1i and Cyclin B1-differential expression. Oncology Letters 2013. In press
[26]	Wang HX, Wang HM, Li QL, Judoson PL. Expression of proteasome subunits low molecular mass polypeptide (LMP) 2 and LMP7 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy. Biol. Reprod. 2004; 71: 1317-24.
[27]	Wang, HX., Wang, HM., Lin, HY., Yang, Q., Zhang, H., Tsang, BK. & Zhu, C. Proteasome subunit LMP2 is required for matrix metalloproteinase-2 and -9 expression and activities in human invasive extravillous trophoblast cell line. J. Cell. Physiol. 2006; 206: 616-623.
[28]	Fu JJ, Lin P, Lv XY, Yan XJ, Wang HX, Zhu C, Tsang BK, Yu XG, Wang H. Low molecular mass polypeptide-2 in human trophoblast: over-expression in hydatidiform moles and possible role in trophoblast cell invasion. Placenta. 2009; 30: 305-12.
[29]	Hayashi T, Horiuchi A, Aburatani H, Yaegashi N, Tonegawa S, Konishi I. A potential diagnostic biomarker: Proteasome LMP2/1i-differential expression in human uterus neoplasm . Nature Precedings 2012; March 2: hdl:10101/npre.2012.7082.1.
[30]	Horiuchi A, Nikaido T, Ito K, Zhai Y, Orii A, Taniguchi S, Toki T, Fujii S. Reduced expression of calponin h1 in lei-omyosarcoma of the uterus. Lab. Invest. 1998; 78: 839-46.
[31]	Horiuchi A, Nikaido T, Taniguchi S, Fujii S. Possible role of calponin h1 as a tumor suppressor in human uterine lei-omyosarcoma. J. Natl. Cancer Inst. 1999; 91: 790-6.
[32]	Zhai YL, Nikaido T, Shiozawa T, Orii A, Fujii S. Expression of cyclins and cyclin-dependent kinases in smooth muscle tumors of the uterus. Intl. J. Cancer 1999; 84: 224-50.
[33]	Ip PP, Cheung AN, Clement PB. Uterine smooth muscle tumors of uncertain malignant potential (STUMP): a clini-copathologic analysis of 16 cases. Am. J. Surg. Pathol. 2009; 33: 992-1005.
[34]	Ip PP, Tse KY, Tam KF. Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy. Adv. Anat. Pathol.2010; 17: 91-112.
[35]	Vajtai I, Sahli R, Kappeler A, Christ ER. Seiler RW. Lei-omyomatoid angiomatous neuroendocrine tumor (LANT) of the pituitary: a distinctive biphasic neoplasm with primitive secretory phenotype and smooth muscle-rich stroma. Acta Neuropathol. 2006; 111: 278-83.
[36]	Sakashita N, Yamada M, Nakagawa T, Yamasaki H, Takeya M. A leiomyomatoid angiomatous neuroendocrine tumor of the myometrium: case study with ultrastructural analysis. Hum. Pathol. 2008; 39: 788-92.
[37]	Avritscher R, Iyer1 RB, Ro J, Whitman G. Lipoleiomyoma of the Uterus. Am. J. Radiol. 2001; 177: 856

Cite This Article

Plain Text BibTeX RIS

APA Style

Takuma Hayashi, Akiko Horiuchi., Nobuo Yaegashi., Tanri Shiozawa., Susumu Tonegawa., et al. (2013). A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Research Journal, 1(1), 1-6. https://doi.org/10.11648/j.crj.20130101.11

Copy | Download

ACS Style

Takuma Hayashi; Akiko Horiuchi.; Nobuo Yaegashi.; Tanri Shiozawa.; Susumu Tonegawa., et al. A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Res. J. 2013, 1(1), 1-6. doi: 10.11648/j.crj.20130101.11

Copy | Download

AMA Style

Takuma Hayashi, Akiko Horiuchi., Nobuo Yaegashi., Tanri Shiozawa., Susumu Tonegawa., et al. A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Res J. 2013;1(1):1-6. doi: 10.11648/j.crj.20130101.11

Copy | Download

@article{10.11648/j.crj.20130101.11,
  author = {Takuma Hayashi and Akiko Horiuchi. and Nobuo Yaegashi. and Tanri Shiozawa. and Susumu Tonegawa. and Ikuo Konishi},
  title = {A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor},
  journal = {Cancer Research Journal},
  volume = {1},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.crj.20130101.11},
  url = {https://doi.org/10.11648/j.crj.20130101.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20130101.11},
  abstract = {Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer 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 uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, to establish a treatment method. Proteasome LMP2/1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/1i expression to be absent in human LMS, but present in human LMA. Therefore, defec-tive-LMP2/1i expression may be one of the risk factors for LMS. LMP2/1i is a potential diagnostic-biomarker under the combination of candidate molecules for uterine mesenchymal tumors, especially uterine LMS, and may be a tar-geted-molecule for a new therapeutic approach. (160 words)},
 year = {2013}
}

Copy | Download

TY  - JOUR
T1  - A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor
AU  - Takuma Hayashi
AU  - Akiko Horiuchi.
AU  - Nobuo Yaegashi.
AU  - Tanri Shiozawa.
AU  - Susumu Tonegawa.
AU  - Ikuo Konishi
Y1  - 2013/05/02
PY  - 2013
N1  - https://doi.org/10.11648/j.crj.20130101.11
DO  - 10.11648/j.crj.20130101.11
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20130101.11
AB  - Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer 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 uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, to establish a treatment method. Proteasome LMP2/1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/1i expression to be absent in human LMS, but present in human LMA. Therefore, defec-tive-LMP2/1i expression may be one of the risk factors for LMS. LMP2/1i is a potential diagnostic-biomarker under the combination of candidate molecules for uterine mesenchymal tumors, especially uterine LMS, and may be a tar-geted-molecule for a new therapeutic approach. (160 words)
VL  - 1
IS  - 1
ER  -

Copy | Download

Author Information

Takuma Hayashi

Dept. of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan
Akiko Horiuchi.

Horiuchi Ladies Clinic, Matsumoto, Nagano 390-0821, Japan
Nobuo Yaegashi.

Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi 980-8574 Japan
Tanri Shiozawa.

Department of Obstetrics and Gynecology, Shinshu University Graduate School of Medicine, Miyagi 390-8621 Japan
Susumu Tonegawa.

Picower Institution and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139-4307 USA
Ikuo Konishi

Dept. of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto-city, Kyoto 606-8507, Japan

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Takuma Hayashi, Akiko Horiuchi., Nobuo Yaegashi., Tanri Shiozawa., Susumu Tonegawa., et al. (2013). A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Research Journal, 1(1), 1-6. https://doi.org/10.11648/j.crj.20130101.11

Copy | Download

ACS Style

Takuma Hayashi; Akiko Horiuchi.; Nobuo Yaegashi.; Tanri Shiozawa.; Susumu Tonegawa., et al. A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Res. J. 2013, 1(1), 1-6. doi: 10.11648/j.crj.20130101.11

Copy | Download

AMA Style

Takuma Hayashi, Akiko Horiuchi., Nobuo Yaegashi., Tanri Shiozawa., Susumu Tonegawa., et al. A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor. Cancer Res J. 2013;1(1):1-6. doi: 10.11648/j.crj.20130101.11

Copy | Download

@article{10.11648/j.crj.20130101.11,
  author = {Takuma Hayashi and Akiko Horiuchi. and Nobuo Yaegashi. and Tanri Shiozawa. and Susumu Tonegawa. and Ikuo Konishi},
  title = {A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor},
  journal = {Cancer Research Journal},
  volume = {1},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.crj.20130101.11},
  url = {https://doi.org/10.11648/j.crj.20130101.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20130101.11},
  abstract = {Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer 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 uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, to establish a treatment method. Proteasome LMP2/1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/1i expression to be absent in human LMS, but present in human LMA. Therefore, defec-tive-LMP2/1i expression may be one of the risk factors for LMS. LMP2/1i is a potential diagnostic-biomarker under the combination of candidate molecules for uterine mesenchymal tumors, especially uterine LMS, and may be a tar-geted-molecule for a new therapeutic approach. (160 words)},
 year = {2013}
}

Copy | Download

TY  - JOUR
T1  - A Novel Diagnostic Marker: Proteasome LMP2/1i-Differential Expression in Human Uterus Mesenchymal Tumor
AU  - Takuma Hayashi
AU  - Akiko Horiuchi.
AU  - Nobuo Yaegashi.
AU  - Tanri Shiozawa.
AU  - Susumu Tonegawa.
AU  - Ikuo Konishi
Y1  - 2013/05/02
PY  - 2013
N1  - https://doi.org/10.11648/j.crj.20130101.11
DO  - 10.11648/j.crj.20130101.11
T2  - Cancer Research Journal
JF  - Cancer Research Journal
JO  - Cancer Research Journal
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2330-8214
UR  - https://doi.org/10.11648/j.crj.20130101.11
AB  - Uterine leiomyosarcoma (LMS) develops more often in the muscle tissue layer 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 uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS, to establish a treatment method. Proteasome LMP2/1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/1i expression to be absent in human LMS, but present in human LMA. Therefore, defec-tive-LMP2/1i expression may be one of the risk factors for LMS. LMP2/1i is a potential diagnostic-biomarker under the combination of candidate molecules for uterine mesenchymal tumors, especially uterine LMS, and may be a tar-geted-molecule for a new therapeutic approach. (160 words)
VL  - 1
IS  - 1
ER  -

Copy | Download