Proteasome LMP2/β1i subunit as biomarker for human uterine leiomyosarcoma

Takuma Hayashi, Akiko Horiuchi, Hiroyuki Aburatani, Osamu Ishiko, Nobuo Yaegashi, Yae Kanai, Dorit Zharhary, Susumu Tonegawa, Ikuo Konishi

Abstract


Uterine leiomyosarcoma (Ut-LMS) develops more frequently in the myometrium of the uterine body than in the uterine cervix. Although the development of gynecological tumors is often correlated with the secretion of female hormones that of Ut-LMS does not, and its risk factor(s) remain unknown. Importantly, a diagnostic biomarker that can distinguish malignant tumor Ut-LMS from benign tumor leiomyoma (LMA), has yet to be established. Therefore, the risk factor(s) associated with Ut-LMS need to be examined in order to establish a diagnosis and clinical treatment method. Mice with a homozygous deficiency for the proteasome b-ring subunit, low-molecular mass polypeptide (LMP)2/b1i spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. In recent studies, we showed that LMP2/b1i expression was absent in human Ut-LMS, but present in other human uterine mesenchymal tumors including uterine LMA. Moreover, LMP2/b1i is also known to negatively regulate human Ut-LMS tumorigenesis. Additional experiments furthermore revealed the differential expression of cyclin E and calponin h1 in human uterine mesenchymal tumors. Therefore, LMP2/b1i is a potential diagnostic biomarker when combined with the candidate molecules, cyclin E and calponin h1 for human Ut-LMS, and may be a targeted molecule for a new therapeutic approach.

---------------------------------------------

Cite this article as: Hayashi T, Horiuchi A Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I. Proteasome LMP2/ß1i subunit as biomarker for human uterine leiomyosarcoma. Int J Cancer Ther Oncol 2014; 2(1):02018.

DOI: http://dx.doi.org/10.14319/ijcto.0201.8


Keywords


LMP2/β1i; Biomarker; Uterin leiomyosarcoma; Leiomyoma; Proteasome

Full Text:

PDF HTML

References


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.

Wu TI, Chang TC, Hsueh S, Hsu KH, Chou HH, Huang HJ, Lai CH. Prognostic factors and impact of adjuvant chemotherapy for uterine leiomyosarcoma. Gynecol Oncol 2006; 100: 166-72.

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 expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma. Cancer 2004; 101: 1455-62.

http://cancer.gov/cancertopics/pdq/treatment/uterinesarcoma/HealthProfessional (Accessed on December 15, 2013)

Kurma RJ. Pathology of the Female Genital Tract, 4th ed. New York, Springer-Verlag 2001; 4: 499.

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.

Lin JF, Slomovitz BM. Uterine sarcoma. Curr Oncol Rep 2008; 10: 512-8.

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.

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.

Konstantinova IM, Tsimokha AS, Mittenberg AG. Role of proteasomes in cellular regulation. Intl Rev Cell Mol Biol 2008; 267: 59–124.

Wang J, Maldonado MA. The Ubiquitin-Proteasome System and Its Role in Inflammatory and Autoimmune Diseases. Cell Mol Immunol 2006; 3: 255–61.

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.

Hayashi T, Faustman DL. Development of spontaneous uterine tumors in low molecular mass polypeptide-2 knockout mice. Cancer Res 2002; 62: 24-7.

Hayashi T, Kobayashi Y, Kohsaka S, Sano K. The 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.

Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura 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.

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 1999; 18: 20-8.

Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura 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 leiomyosarcoma: morphological significance of calponin h1. FEBS Letter 2012; 586: 1824-31.

Hayashi T, Horiuchi A, Konishi I. Tumor growth arrest: involvement of the mutation in the cataritic region of JAK1. Europian Journal of Research in Medical Science 2013; 1: 8-21.

Wang HX, Wang HM, Li QL, Lin HY, Qian D, Zhu C. 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: 1317-1324.

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: 616-23.

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.

Sakashita N, Yamada M, Nakagawa T, Yamasaki H, Takeya M. A leiomyomatoid angiomatous neuroendocrine tumor of the myometrium: case study with ultrastructural analysis. Hum Pathol2008; 39: 788-92.

Avritscher R, Iyer1 RB, Ro J, Whitman G. Lipoleiomyoma of the Uterus. AJR Am J Radiol 2001; 177: 856.




DOI: http://dx.doi.org/10.14319/ijcto.0201.8

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

------------------------------------------------------------

International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.

------------------------------------------------------------

Number of visits since October, 2013
AmazingCounters.com