Literature DB >> 21234586

c-Jun N-terminal kinase is involved in the regulation of proliferation and apoptosis by integrin-linked kinase in human retinoblastoma cells.

Zhen Chen1, Anhuai Yang, Chong Xu, Yiqiao Xing, Wenrong Gong, Junping Li.   

Abstract

PURPOSE: To determine the presence of integrin-linked kinase (ILK) in tissue samples of retinoblastoma patients, and to explore the function of ILK in human Y79 retinoblastoma cells.
METHODS: The expression of ILK was studied in samples of retinoblastoma patients by immunohistochemistry. In vitro, specific small interfering RNA (siRNA) targeting ILK was transfected into Y79 retinoblastoma cells using liposome. Silencing of ILK expression was measured by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR and Western blotting assays. Then the regulation of cell proliferation and apoptosis was assessed by Cell Counting Kit-8(CCK-8), Annexin V-FITC/ propidium iodide (PI) immunofluorescence, and flow cytometry assays. Furthermore, the involvement of c-Jun N-terminal kinase signal pathway was tested by JNK signal transduction inhibitor assay.
RESULTS: Positive staining for ILK was detected in 15 of the 17 retinoblastoma tissue samples. Specific siRNA targeting ILK significantly silenced ILK expression in Y79 retinoblastoma cells, as confirmed by RT-PCR, real-time PCR and Western blotting assays (P < 0.01). This was accompanied by decreased cell proliferation (P < 0.05) and enhanced apoptosis (P < 0.01). The phosphorylation status of JNK and c-Jun was constitutively activated by ILK siRNA (P < 0.01), and JNK inhibitor simultaneously reversed the effects on cell proliferation and apoptosis induced by ILK siRNA.
CONCLUSION: Our results demonstrated that ILK promoted proliferation and suppressed apoptosis via repressing phosphorylations of the JNK signal pathway in human retinoblastoma cells. This might provide a potential therapeutic target in the treatment of this deadly disease.

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Year:  2011        PMID: 21234586     DOI: 10.1007/s00417-010-1607-3

Source DB:  PubMed          Journal:  Graefes Arch Clin Exp Ophthalmol        ISSN: 0721-832X            Impact factor:   3.117


  38 in total

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Authors:  Gary L Johnson; Kazuhiro Nakamura
Journal:  Biochim Biophys Acta       Date:  2007-01-04

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3.  JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.

Authors:  B Dérijard; M Hibi; I H Wu; T Barrett; B Su; T Deng; M Karin; R J Davis
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Review 4.  AP-1 as a regulator of cell life and death.

Authors:  Eitan Shaulian; Michael Karin
Journal:  Nat Cell Biol       Date:  2002-05       Impact factor: 28.824

Review 5.  Integrin-linked kinase: a cancer therapeutic target unique among its ILK.

Authors:  Gregory Hannigan; Armelle A Troussard; Shoukat Dedhar
Journal:  Nat Rev Cancer       Date:  2005-01       Impact factor: 60.716

Review 6.  Retinoblastoma: review of current management.

Authors:  Murali Chintagumpala; Patricia Chevez-Barrios; Evelyn A Paysse; Sharon E Plon; Richard Hurwitz
Journal:  Oncologist       Date:  2007-10

7.  Expression of integrin-linked kinase is increased in differentiated cells.

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Authors:  Dong Xie; Dong Yin; Xiangjun Tong; James O'Kelly; Akio Mori; Carl Miller; Keith Black; Dorina Gui; Johathan W Said; H Phillip Koeffler
Journal:  Cancer Res       Date:  2004-03-15       Impact factor: 12.701

9.  Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency.

Authors:  Isabelle Quélo; Claude Gauthier; Gregory E Hannigan; Shoukat Dedhar; René St-Arnaud
Journal:  J Biol Chem       Date:  2004-08-06       Impact factor: 5.157

10.  Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation.

Authors:  S Persad; A A Troussard; T R McPhee; D J Mulholland; S Dedhar
Journal:  J Cell Biol       Date:  2001-06-11       Impact factor: 10.539

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  3 in total

1.  Integrin-linked kinase regulates senescence in an Rb-dependent manner in cancer cell lines.

Authors:  Rose Duminuco; Jake W Noble; Joseph Goody; Manju Sharma; Bruce R Ksander; Calvin D Roskelley; Michael E Cox; Julia Mills
Journal:  Cell Cycle       Date:  2015       Impact factor: 4.534

2.  Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue Microarrays as a Medium-Throughput, Quantitative Method for Measuring the Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition in an In Vivo Model of Cancer.

Authors:  Jessica Kalra; Weislawa H Dragowska; Marcel B Bally
Journal:  J Histochem Cytochem       Date:  2015-05-04       Impact factor: 2.479

3.  Regulation of mitotic cytoskeleton dynamics and cytokinesis by integrin-linked kinase in retinoblastoma cells.

Authors:  William K A Sikkema; Arend Strikwerda; Manju Sharma; Kiran Assi; Baljinder Salh; Michael E Cox; Julia Mills
Journal:  PLoS One       Date:  2014-06-09       Impact factor: 3.240

  3 in total

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