Receptor-like protein tyrosine phosphatase κ negatively regulates the apoptosis of prostate cancer cells via the JNK pathway

Sun,Ping-Hui; Ye,Lin; Mason,Malcolm  D.; Jiang,Wen  G.

doi:10.3892/ijo.2013.2082

Receptor-like protein tyrosine phosphatase κ negatively regulates the apoptosis of prostate cancer cells via the JNK pathway

Authors:
- Ping-Hui Sun
- Lin Ye
- Malcolm D. Mason
- Wen G. Jiang
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Affiliations: Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
Published online on: August 29, 2013 https://doi.org/10.3892/ijo.2013.2082
Pages: 1560-1568

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Abstract

Receptor-like protein tyrosine phosphatase κ (PTPRK) has been indicated as a putative tumour suppressor in primary central nervous system lymphomas and colorectal cancer. The present study investigated the expression of PTPRK in prostate cancer and the biological impact of PTPRK on prostate cancer cells. The expression of the PTPRK protein and transcript in prostate cancer was examined using IHC and PCR. Knockdown of PTPRK in prostate cancer cells was performed using a specific anti-PTPRK transgene. The impact of PTPRK knockdown on prostate cancer cells was evaluated using in vitro cell models and the apoptosis was analysed using flow cytometry. PTPRK expression was increased in prostate cancer tissues and knockdown of PTPRK in PC-3 cells suppressed the in vitro cell growth in which an increased apoptotic population was seen. Accompanied with the knockdown of PTPRK, increased expression of caspase-3, caspase-8 and p53, and a decreased ID1 expression were evident in the cells. Furthermore, an increased tyrosine phosphorylated c-Jun N-terminal kinase (JNK) was seen in the PTPRK knockdown cells. The effect on apoptosis was diminished by a JNK inhibitor. In conclusion, PTPRK knockdown resulted in increased apoptosis leading to the inhibition of in vitro growth of prostate cancer cells. PTPRK is a key factor in coordinating apoptosis via the regulation of MAPK pathways, in particular the JNK pathway in prostate cancer cells.

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1.	Wallach D, Kang TB and Kovalenko A: The extrinsic cell death pathway and the elan mortel. Cell Death Differ. 15:1533–1541. 2008. View Article : Google Scholar : PubMed/NCBI
2.	Wajant H and Scheurich P: TNFR1-induced activation of the classical NF-κB pathway. FEBS J. 278:862–876. 2011.
3.	Halle M, Liu YC, Hardy S, et al: Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response. Mol Cell Biol. 27:1172–1190. 2007. View Article : Google Scholar
4.	Akasaki Y, Liu G, Matundan HH, et al: A peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells. J Biol Chem. 281:6165–6174. 2006. View Article : Google Scholar
5.	Gu F, Nguyen DT, Stuible M, Dube N, Tremblay ML and Chevet E: Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem. 279:49689–49693. 2004. View Article : Google Scholar : PubMed/NCBI
6.	Sangwan V, Paliouras GN, Cheng A, Dube N, Tremblay ML and Park M: Protein-tyrosine phosphatase 1B deficiency protects against Fas-induced hepatic failure. J Biol Chem. 281:221–228. 2006. View Article : Google Scholar : PubMed/NCBI
7.	Gupta S, Radha V, Sudhakar C and Swarup G: A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis. FEBS Lett. 532:61–66. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Radha V, Sudhakar C and Swarup G: Induction of p53 dependent apoptosis upon overexpression of a nuclear protein tyrosine phosphatase. FEBS Lett. 453:308–312. 1999. View Article : Google Scholar : PubMed/NCBI
9.	Jiang WG, Watkins G, Fodstad O, Douglas-Jones A, Mokbel K and Mansel RE: Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer. Endocr Relat Cancer. 11:781–791. 2004. View Article : Google Scholar : PubMed/NCBI
10.	Zuker M: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31:3406–3415. 2003. View Article : Google Scholar : PubMed/NCBI
11.	Jiang WG, Davies G, Martin TA, et al: Targeting matrilysin and its impact on tumor growth in vivo: the potential implications in breast cancer therapy. Clin Cancer Res. 11:6012–6019. 2005. View Article : Google Scholar : PubMed/NCBI
12.	Cady FM, O’Neill BP, Law ME, et al: Del(6)(q22) and BCL6 rearrangements in primary CNS lymphoma are indicators of an aggressive clinical course. J Clin Oncol. 26:4814–4819. 2008. View Article : Google Scholar : PubMed/NCBI
13.	Nakamura M, Kishi M, Sakaki T, et al: Novel tumor suppressor loci on 6q22-23 in primary central nervous system lymphomas. Cancer Res. 63:737–741. 2003.PubMed/NCBI
14.	Starr TK, Allaei R, Silverstein KA, et al: A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science. 323:1747–1750. 2009. View Article : Google Scholar : PubMed/NCBI
15.	Lu J, Li Q, Donadel G, Notkins AL and Lan MS: Profile and differential expression of protein tyrosine phosphatases in mouse pancreatic islet tumor cell lines. Pancreas. 16:515–520. 1998. View Article : Google Scholar : PubMed/NCBI
16.	Julien SG, Dube N, Hardy S and Tremblay ML: Inside the human cancer tyrosine phosphatome. Nat Rev Cancer. 11:35–49. 2011. View Article : Google Scholar : PubMed/NCBI
17.	Halle M, Tremblay ML and Meng TC: Protein tyrosine phosphatases: emerging regulators of apoptosis. Cell Cycle. 6:2773–2781. 2007. View Article : Google Scholar : PubMed/NCBI
18.	Lee ST, Wong PF, Cheah SC and Mustafa MR: Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells. PLoS One. 6:e189152011. View Article : Google Scholar : PubMed/NCBI
19.	Marsh HN, Dubreuil CI, Quevedo C, et al: SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase. J Cell Biol. 163:999–1010. 2003. View Article : Google Scholar : PubMed/NCBI
20.	Amoui M, Sheng MH, Chen ST, Baylink DJ and Lau KH: A transmembrane osteoclastic protein-tyrosine phosphatase regulates osteoclast activity in part by promoting osteoclast survival through c-Src-dependent activation of NFkappaB and JNK2. Arch Biochem Biophys. 463:47–59. 2007. View Article : Google Scholar
21.	Pietsch EC, Sykes SM, McMahon SB and Murphy ME: The p53 family and programmed cell death. Oncogene. 27:6507–6521. 2008. View Article : Google Scholar : PubMed/NCBI
22.	Aimola P, Carmignani M, Volpe AR, et al: Cadmium induces p53-dependent apoptosis in human prostate epithelial cells. PLoS One. 7:e336472012. View Article : Google Scholar : PubMed/NCBI
23.	Cao H, Feng Q, Xu W, et al: Genipin induced apoptosis associated with activation of the c-Jun NH2-terminal kinase and p53 protein in HeLa cells. Biol Pharm Bull. 33:1343–1348. 2010. View Article : Google Scholar : PubMed/NCBI
24.	Ling MT, Wang X, Ouyang XS, Xu K, Tsao SW and Wong YC: Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells. Oncogene. 22:4498–4508. 2003. View Article : Google Scholar : PubMed/NCBI
25.	Peng X, Wang Y, Kolli S, et al: Physical and functional interaction between the ID1 and p65 for activation of NF-κB. Am J Physiol Cell Physiol. 303:C267–C277. 2012.PubMed/NCBI