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Published in: Medical Oncology 4/2012

01-12-2012 | Original Paper

Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27

Authors: Ling Gao, Shuo Huang, Wenhao Ren, Lu Zhao, Jingwei Li, Keqian Zhi, Yincheng Zhang, Hong Qi, Chen Huang

Published in: Medical Oncology | Issue 4/2012

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Abstract

The Jun activation domain-binding protein 1 (Jab1) may be involved in degradation of the cyclin-dependent kinase inhibitor p27, but it has not been clarified. In this study, we observed expression levels of Jab1 and p27 in oral squamous cell carcinoma (OSCC) and normal oral mucosa tissue and evaluated whether the Jab1 expression is correlated with p27 protein levels and how it is clinically relevant OSCC. The clinicopathological features and immunohistochemical expression levels of Jab1 and p27 proteins were immunohistochemically studied in 206 specimens from patients who underwent surgical resection for OSCC. Survival analyses were performed by using the Kaplan–Meier method. Jab1 overexpression was detected in 83% (171 of 206) of OSCCs and 19% (4 of 21) of normal oral mucosa. While p27 expression was 60% in OSCCs. We found an inverse correlation between Jab1 and p27 expression levels (P < 0.001). Kaplan–Meier survival analysis showed that Jab1 overexpression and p27 low expression were significantly associated with poor prognosis of patients. Our findings suggest that Jab1 expression is inversely correlated with p27 expression levels, suggesting that Jab1 overexpression contributes to pathogenesis of OSCC by degradating p27 expression. Furthermore, control of Jab1 could be a novel target of therapy in OSCCs.
Literature
1.
go back to reference Parkin D, L r E, Muir C. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988;41(2):184–97.PubMedCrossRef Parkin D, L r E, Muir C. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988;41(2):184–97.PubMedCrossRef
2.
go back to reference Khuri FR, Shin DM, Glisson BS, Lippman SM, Hong WK (eds). Treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck: current status and future directions 2000. Khuri FR, Shin DM, Glisson BS, Lippman SM, Hong WK (eds). Treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck: current status and future directions 2000.
3.
go back to reference Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001;345(26):1890–900.PubMedCrossRef Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001;345(26):1890–900.PubMedCrossRef
4.
go back to reference Choi S, Myers J. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008;87(1):14.PubMedCrossRef Choi S, Myers J. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008;87(1):14.PubMedCrossRef
5.
go back to reference Claret FX, Hibi M, Dhut S, Toda T, Karin M. A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. 1996. Claret FX, Hibi M, Dhut S, Toda T, Karin M. A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. 1996.
6.
go back to reference Schwechheimer C, Deng XW. COP9 signalosome revisited: a novel mediator of protein degradation. Trends Cell Biol. 2001;11(10):420–6.PubMedCrossRef Schwechheimer C, Deng XW. COP9 signalosome revisited: a novel mediator of protein degradation. Trends Cell Biol. 2001;11(10):420–6.PubMedCrossRef
7.
go back to reference Chamovitz DA, Segal D. JAB1/CSN5 and the COP9 signalosome: a complex situation. EMBO Rep. 2001;2(2):96.PubMedCrossRef Chamovitz DA, Segal D. JAB1/CSN5 and the COP9 signalosome: a complex situation. EMBO Rep. 2001;2(2):96.PubMedCrossRef
8.
go back to reference Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 1994;78(1):67–74.PubMedCrossRef Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 1994;78(1):67–74.PubMedCrossRef
9.
go back to reference Yoshida A, Yoneda-Kato N, Panattoni M, Pardi R, Kato J. CSN5/Jab1 controls multiple events in the mammalian cell cycle. FEBS Lett. 2010. Yoshida A, Yoneda-Kato N, Panattoni M, Pardi R, Kato J. CSN5/Jab1 controls multiple events in the mammalian cell cycle. FEBS Lett. 2010.
10.
go back to reference Tomoda K, Kubota Y, Kato J. Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature. 1999;398(6723):160–5.PubMedCrossRef Tomoda K, Kubota Y, Kato J. Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature. 1999;398(6723):160–5.PubMedCrossRef
13.
go back to reference Wang Y, Cheng C, Ji Y, Zhao Y, Zou L, Shen A. Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma. J Cancer Res Clin Oncol. 2009;135(7):951–9.PubMedCrossRef Wang Y, Cheng C, Ji Y, Zhao Y, Zou L, Shen A. Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma. J Cancer Res Clin Oncol. 2009;135(7):951–9.PubMedCrossRef
14.
go back to reference Berg JP, Zhou Q, Breuhahn K, Schirmacher P, Patil MA, Chen X, et al. Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1: influence on proliferation in hepatocellular carcinoma. Hum Pathol. 2007;38(11):1621–7.PubMedCrossRef Berg JP, Zhou Q, Breuhahn K, Schirmacher P, Patil MA, Chen X, et al. Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1: influence on proliferation in hepatocellular carcinoma. Hum Pathol. 2007;38(11):1621–7.PubMedCrossRef
15.
go back to reference Kouvaraki MA, Rassidakis GZ, Tian L, Kumar R, Kittas C, Claret FX. Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27Kip1. Cancer Res. 2003;63(11):2977.PubMed Kouvaraki MA, Rassidakis GZ, Tian L, Kumar R, Kittas C, Claret FX. Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27Kip1. Cancer Res. 2003;63(11):2977.PubMed
16.
go back to reference Shintani S, Li C, Mihara M, Hino S, Nakashiro K, Hamakawa H. Skp2 and jab1 expression are associated with inverse expression of p27 < sup > KIP1 </sup > and poor prognosis in oral squamous cell carcinomas. Oncology. 2000;65(4):355–62.CrossRef Shintani S, Li C, Mihara M, Hino S, Nakashiro K, Hamakawa H. Skp2 and jab1 expression are associated with inverse expression of p27 < sup > KIP1 </sup > and poor prognosis in oral squamous cell carcinomas. Oncology. 2000;65(4):355–62.CrossRef
17.
go back to reference Kouvaraki MA, Korapati AL, Rassidakis GZ, Tian L, Zhang Q, Chiao P, et al. Potential role of Jun activation domain? binding protein 1 as a negative regulator of p27kip1 in pancreatic adenocarcinoma. Cancer Res. 2006;66(17):8581.PubMedCrossRef Kouvaraki MA, Korapati AL, Rassidakis GZ, Tian L, Zhang Q, Chiao P, et al. Potential role of Jun activation domain? binding protein 1 as a negative regulator of p27kip1 in pancreatic adenocarcinoma. Cancer Res. 2006;66(17):8581.PubMedCrossRef
18.
go back to reference Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, et al. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem. 2002;277(3):2302.PubMedCrossRef Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, et al. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem. 2002;277(3):2302.PubMedCrossRef
19.
go back to reference Ahn J, Hong SA, Lee S, Kim J, Oh YS, Park S, et al. Cytoplasmic localization of Jab1 and p27 Kip1 might be associated with invasiveness of papillary thyroid carcinoma. Endocr J. 2009;56(5):707.PubMedCrossRef Ahn J, Hong SA, Lee S, Kim J, Oh YS, Park S, et al. Cytoplasmic localization of Jab1 and p27 Kip1 might be associated with invasiveness of papillary thyroid carcinoma. Endocr J. 2009;56(5):707.PubMedCrossRef
20.
go back to reference Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tai Y, et al. Jab1 expression is associated with inverse expression of p27kip1 and poor prognosis in epithelial ovarian tumors. Clin Cancer Res. 2001;7(12):4130.PubMed Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tai Y, et al. Jab1 expression is associated with inverse expression of p27kip1 and poor prognosis in epithelial ovarian tumors. Clin Cancer Res. 2001;7(12):4130.PubMed
21.
go back to reference Korbonits M, Chahal HS, Kaltsas G, Jordan S, Urmanova Y, Khalimova Z, et al. Expression of phosphorylated p27Kip1 protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab. 2002;87(6):2635.PubMedCrossRef Korbonits M, Chahal HS, Kaltsas G, Jordan S, Urmanova Y, Khalimova Z, et al. Expression of phosphorylated p27Kip1 protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab. 2002;87(6):2635.PubMedCrossRef
22.
go back to reference Wang F, Wang Y, Yu X, Yang D, Wang Z, Lu C, et al. Significance of Jab1 expression in human esophageal squamous cell carcinoma. J Clin Gastroenterol. 2009;43(6):520.PubMedCrossRef Wang F, Wang Y, Yu X, Yang D, Wang Z, Lu C, et al. Significance of Jab1 expression in human esophageal squamous cell carcinoma. J Clin Gastroenterol. 2009;43(6):520.PubMedCrossRef
23.
go back to reference Hashimoto N, Yachida S, Okano K, Wakabayashi H, Imaida K, Kurokohchi K, et al. Immunohistochemically detected expression of p27 kip1 and skp2 predicts survival in patients with intrahepatic cholangiocarcinomas. Ann Surg Oncol. 2009;16(2):395–403.PubMedCrossRef Hashimoto N, Yachida S, Okano K, Wakabayashi H, Imaida K, Kurokohchi K, et al. Immunohistochemically detected expression of p27 kip1 and skp2 predicts survival in patients with intrahepatic cholangiocarcinomas. Ann Surg Oncol. 2009;16(2):395–403.PubMedCrossRef
24.
go back to reference Kuo MYP, Hsu HY, Kok SH, Kuo RC, Yang H, Hahn LJ, et al. Prognostic role of p27Kip1 expression in oral squamous cell carcinoma in Taiwan. Oral Oncol. 2002;38(2):172–8.PubMedCrossRef Kuo MYP, Hsu HY, Kok SH, Kuo RC, Yang H, Hahn LJ, et al. Prognostic role of p27Kip1 expression in oral squamous cell carcinoma in Taiwan. Oral Oncol. 2002;38(2):172–8.PubMedCrossRef
25.
go back to reference Shimada M, Kitagawa K, Dobashi Y, Isobe T, Hattori T, Uchida C, et al. High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers. Cancer Sci. 2009;100(5):866–72.PubMedCrossRef Shimada M, Kitagawa K, Dobashi Y, Isobe T, Hattori T, Uchida C, et al. High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers. Cancer Sci. 2009;100(5):866–72.PubMedCrossRef
26.
go back to reference Esteva FJ, Sahin AA, Rassidakis GZ, Yuan LXH, Smith TL, Yang Y, et al. Jun activation domain binding protein 1 expression is associated with low p27kip1levels in node-negative breast cancer. Clin Cancer Res. 2003;9(15):5652.PubMed Esteva FJ, Sahin AA, Rassidakis GZ, Yuan LXH, Smith TL, Yang Y, et al. Jun activation domain binding protein 1 expression is associated with low p27kip1levels in node-negative breast cancer. Clin Cancer Res. 2003;9(15):5652.PubMed
Metadata
Title
Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27
Authors
Ling Gao
Shuo Huang
Wenhao Ren
Lu Zhao
Jingwei Li
Keqian Zhi
Yincheng Zhang
Hong Qi
Chen Huang
Publication date
01-12-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 4/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0177-0

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