Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2009

01.07.2009 | Original Paper

Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma

verfasst von: You Wang, Yuchan Wang, Chun Cheng, Yuhong Ji, Yueming Zhao, Lin Zou, Aiguo Shen

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of the present study was to examine whether Jab1 expression is correlated with p27 protein and its phosphorylation status as well as how it might be clinically relevant in epithelial ovarian carcinoma. Using ovarian carcinoma cell line HO-8910 to confirm and extend the findings.

Methods

Immunohistochemical and Western blot analysis were done in 70 cases of epithelial ovarian cacinoma and HO-8910 cells.

Results

Jab1 overexpression was detected in 84.3% (59 of 70) of malignant tumors and 31.6% (6 of 19) of benign tumors. A positive correlation between Jab1 and cytoplasmic p27 as well as Ser10 phosphorylated p27 was found in malignant ovarian tumors. In addition, patients displaying overexpression of Jab1, cytoplasmic p27 and Ser10 phosphorylated p27 were significantly associated with unfavorable clinicopathologic variables. Transfection with Jab1 in HO-8910 cells resulted in decreased p27 expression and this reduction was sensitive to 26S proteasome inhibitors. Overexpression of Jab1 caused p27 nuclear export and dissociate from Cdk2/Cyclin complex. What is more, increased expression of a phosphorylated histone H1 in the immune-complex obtained from Jab1 transfected HO-8910 cells was also observed.

Conclusions

Jab1, as a negative regulator of p27, may be associated with the progression and prognosis of epithelial ovarian tumors.
Literatur
Zurück zum Zitat Esteva FJ, Sahin AA, Rassidakis GZ et al (2003) Jun activation domain binding protein 1 expression is associated with low p27(Kip1) levels in node-negative breast cancer. Clin Cancer Res 9:5652–5659PubMed Esteva FJ, Sahin AA, Rassidakis GZ et al (2003) Jun activation domain binding protein 1 expression is associated with low p27(Kip1) levels in node-negative breast cancer. Clin Cancer Res 9:5652–5659PubMed
Zurück zum Zitat Guan X, Chen L, Wang J et al (2006) Mutations of phosphorylation sites Ser10 and Thr187 of p27Kip1 abolish cytoplasmic redistribution but do not abrogate G0/1 phase arrest in the HepG2 cell line. Biochem Biophys Res Commun 347:601–607. doi:10.1016/j.bbrc.2006.06.114 PubMedCrossRef Guan X, Chen L, Wang J et al (2006) Mutations of phosphorylation sites Ser10 and Thr187 of p27Kip1 abolish cytoplasmic redistribution but do not abrogate G0/1 phase arrest in the HepG2 cell line. Biochem Biophys Res Commun 347:601–607. doi:10.​1016/​j.​bbrc.​2006.​06.​114 PubMedCrossRef
Zurück zum Zitat Ishida N, Kitagawa M, Hatakeyama S et al (2000) Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J. Biol. Chem 275:25146–25154PubMedCrossRef Ishida N, Kitagawa M, Hatakeyama S et al (2000) Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J. Biol. Chem 275:25146–25154PubMedCrossRef
Zurück zum Zitat Ozols RF (2002) Update on the management of ovarian cancer. Cancer J 8:S22–S30PubMed Ozols RF (2002) Update on the management of ovarian cancer. Cancer J 8:S22–S30PubMed
Zurück zum Zitat Korbonits M, Chahal HS, Kaltsas G et al (2002) Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab 87:2635–2643. doi:10.1210/jc.87.6.2635 PubMedCrossRef Korbonits M, Chahal HS, Kaltsas G et al (2002) Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors. J Clin Endocrinol Metab 87:2635–2643. doi:10.​1210/​jc.​87.​6.​2635 PubMedCrossRef
Zurück zum Zitat Kouvaraki MA, Rassidakis GZ, Tian L et al (2003) Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1). Cancer Res 63:2977–2981PubMed Kouvaraki MA, Rassidakis GZ, Tian L et al (2003) Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1). Cancer Res 63:2977–2981PubMed
Zurück zum Zitat Lenferink AE, Busse D, Flanagan WM et al (2001) ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple signaling pathways. Cancer Res 61:6583–6591PubMed Lenferink AE, Busse D, Flanagan WM et al (2001) ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple signaling pathways. Cancer Res 61:6583–6591PubMed
Zurück zum Zitat Liang J, Zubovitz J, Petrocelli T et al (2002) PKB/AKT phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 8(10):1153–1160. doi:10.1038/nm761 PubMedCrossRef Liang J, Zubovitz J, Petrocelli T et al (2002) PKB/AKT phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 8(10):1153–1160. doi:10.​1038/​nm761 PubMedCrossRef
Zurück zum Zitat Polyak K, Lee MH, Erdjument-Bromage H et al (1994) Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 789:59–66. doi:10.1016/0092-8674(94)90572-X CrossRef Polyak K, Lee MH, Erdjument-Bromage H et al (1994) Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 789:59–66. doi:10.​1016/​0092-8674(94)90572-X CrossRef
Zurück zum Zitat Shin I, Yakes MF, Rojo F et al (2002) PKB/Akt mediates cell-cycle progression by phosphorylation of p27kip1 at threonine 157 and modulation of its cellular localization. Nat Med 8:1145–1152. doi:10.1038/nm759 PubMedCrossRef Shin I, Yakes MF, Rojo F et al (2002) PKB/Akt mediates cell-cycle progression by phosphorylation of p27kip1 at threonine 157 and modulation of its cellular localization. Nat Med 8:1145–1152. doi:10.​1038/​nm759 PubMedCrossRef
Zurück zum Zitat Shintani S, Li C, Mihara M et al (2003) Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology 65:355–362. doi:10.1159/000074649 PubMedCrossRef Shintani S, Li C, Mihara M et al (2003) Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology 65:355–362. doi:10.​1159/​000074649 PubMedCrossRef
Zurück zum Zitat Slingerland J, Pagano M (2000) Regulation of the cdk inhibitor p27 and its deregulation in cancer. J Cell Physiol 183:10–17. doi:10.1002/(SICI)1097-4652(200004)183:1<10::AID-JCP2>3.0.CO;2-IPubMedCrossRef Slingerland J, Pagano M (2000) Regulation of the cdk inhibitor p27 and its deregulation in cancer. J Cell Physiol 183:10–17. doi:10.1002/(SICI)1097-4652(200004)183:1<10::AID-JCP2>3.0.CO;2-IPubMedCrossRef
Zurück zum Zitat Sui L, Dong Y, Ohno M et al (2001) Jab1 expression is associated with inverse expression of p27(kip1) and poor prognosis in epithelial ovarian tumors. Clin Cancer Res 7:4130–4135PubMed Sui L, Dong Y, Ohno M et al (2001) Jab1 expression is associated with inverse expression of p27(kip1) and poor prognosis in epithelial ovarian tumors. Clin Cancer Res 7:4130–4135PubMed
Zurück zum Zitat Viglietto G, Motti ML, Bruni P et al (2002) Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27kip1 by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 8:1136–1144. doi:10.1038/nm762 PubMedCrossRef Viglietto G, Motti ML, Bruni P et al (2002) Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27kip1 by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 8:1136–1144. doi:10.​1038/​nm762 PubMedCrossRef
Metadaten
Titel
Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma
verfasst von
You Wang
Yuchan Wang
Chun Cheng
Yuhong Ji
Yueming Zhao
Lin Zou
Aiguo Shen
Publikationsdatum
01.07.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0531-y

Weitere Artikel der Ausgabe 7/2009

Journal of Cancer Research and Clinical Oncology 7/2009 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.