Phosphorylation of BMK1 induces prostatic carcinoma cell proliferation by promoting entry into the S phase of the cell cycle

Xiong,Ying; Zhang,Luying; Wang,Tao

doi:10.3892/ol.2015.3909

Phosphorylation of BMK1 induces prostatic carcinoma cell proliferation by promoting entry into the S phase of the cell cycle

Authors:
- Ying Xiong
- Luying Zhang
- Tao Wang
View Affiliations

Affiliations: Department of Urology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China, Division of Anatomy, Hubei College of Chinese Medicine, Jingzhou, Hubei 434100, P.R. China
Published online on: November 10, 2015 https://doi.org/10.3892/ol.2015.3909
Pages: 99-104
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Big mitogen-activated protein kinase 1 (BMK1) is activated by mitogens and oncogenic signals, and is strongly implicated in tumorigenesis. In the present study, it was demonstrated that the activation of BMK1, but not extracellular signal-regulated kinase (ERK)1/2, can induce proliferation in prostate cancer cells. It was found that the proliferation of epidermal growth factor (EGF)‑treated cells was accelerated by 40% compared with non‑treated cells using a CCK8 assay. In addition, cell cycle analysis using flow cytometry showed that the proportion of cells in the S phase increased significantly in the BMK1‑activated PC‑3 cells, suggesting that the activation of BMK1 promotes entry into the S phase of the cell cycle in prostate cancer cells. Furthermore, western blot analysis indicated that EGF‑mediated activation of BMK1, but not ERK1/2, participates in the proliferation and cell cycle regulation in prostate cancer cells. Furthermore, the effects of cell cycle regulation by the activation of BMK1 were associated with the increased expression levels of cyclin A and cyclin E, whereas the expression of cyclin B and cyclin D1 was unchanged in this process. Therefore, the present study demonstrated that the activation of BMK1 can induce proliferation by promoting entry into the S phase through the upregulation of cyclin A and cyclin E expression levels in prostate cancer cells.

View Figures

View References

1	Debes JD and Tindall DJ: Mechanisms of androgen-refractory prostate cancer. N Engl J Med. 351:1488–1490. 2004. View Article : Google Scholar : PubMed/NCBI
2	Schröder FH: Progress in understanding androgen-independent prostate cancer (AIPC): A review of potential endocrine-mediated mechanisms. Eur Urol. 53:1129–1137. 2008. View Article : Google Scholar : PubMed/NCBI
3	Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI
4	Raman M, Chen W and Cobb MH: Differential regulation and properties of MAPKs. Oncogene. 26:3100–3112. 2007. View Article : Google Scholar : PubMed/NCBI
5	Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI
6	Lee JD, Ulevitch RJ and Han J: Primary structure of BMK1: A new mammalian map kinase. Biochem Biophys Res Commun. 213:715–724. 1995. View Article : Google Scholar : PubMed/NCBI
7	Weldon CB, Scandurro AB, Rolfe KW, Clayton JL, Elliott S, Butler NN, Melnik LI, Alam J, McLachlan JA and Jaffe BM: Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray. Surgery. 132:293–301. 2002. View Article : Google Scholar : PubMed/NCBI
8	Esparis-Ogando A, Díaz-Rodriguez E, Montero JC, Yuste L, Crespo P and Pandiella A: Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2. Mol Cell Biol. 22:270–285. 2002. View Article : Google Scholar : PubMed/NCBI
9	Mehta PB, Jenkins BL, McCarthy L, Thilak L, Robson CN, Neal DE and Leung HY: MEK5 overexpression is associated with metastatic prostate cancer and stimulates proliferation, MMP-9 expression and invasion. Oncogene. 22:1381–1389. 2003. View Article : Google Scholar : PubMed/NCBI
10	Hayashi M and Lee JD: Role of the BMK1/ERK5 signaling pathway: Lessons from knockout mice. J Mol Med (Berl). 82:800–808. 2004. View Article : Google Scholar : PubMed/NCBI
11	Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ and Lee JD: Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 395:713–716. 1998. View Article : Google Scholar : PubMed/NCBI
12	Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y and Lee JD: BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase. J Biol Chem. 276:8631–8634. 2001. View Article : Google Scholar : PubMed/NCBI
13	Cameron SJ, Abe J, Malik S, Che W and Yang J: Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation. J Biol Chem. 279:1506–1512. 2004. View Article : Google Scholar : PubMed/NCBI
14	John PC, Mews M and Moore R: Cyclin/Cdk complexes: Their involvement in cell cycle progression and mitotic division. Protoplasma. 216:119–142. 2001. View Article : Google Scholar : PubMed/NCBI
15	Greenlee RT, Hill-Harmon MB, Murray T and Thun M: Cancer statistics, 2001. CA Cancer J Clin. 51:15–36. 2001. View Article : Google Scholar : PubMed/NCBI
16	Yang Q, Deng X, Lu B, Cameron M, Fearns C, Patricelli MP, Yates JR III, Gray NS and Lee JD: Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 18:258–267. 2010. View Article : Google Scholar : PubMed/NCBI
17	Hayashi M, Fearns C, Eliceiri B, Yang Y and Lee JD: Big mitogen-activated protein kinase 1/extracellular signal-regulated kinase 5 signaling pathway is essential for tumor-associated angiogenesis. Cancer Res. 65:7699–7706. 2005.PubMed/NCBI
18	Pi X, Garin G, Xie L, Zheng Q, Wei H, Abe J, Yan C and Berk BC: BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alpha. Circ Res. 96:1145–1151. 2005. View Article : Google Scholar : PubMed/NCBI
19	Sawhney RS, Liu W and Brattain MG: A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via Fak signaling. J Cell Physiol. 219:152–161. 2009. View Article : Google Scholar : PubMed/NCBI
20	Sticht C, Freier K, Knöpfle K, Flechtenmacher C, Pungs S, Hofele C, Hahn M, Joos S and Lichter P: Activation of MAP kinase signaling through ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC). Neoplasia. 10:462–470. 2008. View Article : Google Scholar : PubMed/NCBI
21	Zhou C, Nitschke AM, Xiong W, Zhang Q, Tang Y, Bloch M, Elliott S, Zhu Y, Bazzone L and Yu D: Proteomic analysis of tumor necrosis factor-alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype. Breast Cancer Res. 10:R1052008. View Article : Google Scholar : PubMed/NCBI
22	Chatterjee A, Chatterjee U and Ghosh MK: Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: Implications in human prostate cancer. Cell Death Dis. 4:e5432013. View Article : Google Scholar : PubMed/NCBI