Novel Insight into Differential Gene Expression and Clinical Significance of Dopamine Receptors, COMT, and IL6 in BPH and Prostate Cancer

Author(s): Fatemeh Akbarian, Maryam Abolhasani, Farid Dadkhah, Farrokh Asadi, Ghasem Ahangari*.

Journal Name: Current Molecular Medicine

Volume 19 , Issue 8 , 2019

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Abstract:

Background: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the most prevalent diseases in male population, implicated with fundamental differences between benign and malignant growth of prostate cells. An imbalance through a network of nervous, endocrine, and immune systems initiate a signal of altered growth from the brain to the prostate gland, leading to adverse effects such as inflammation.

Objective: The aim of this study was to evaluate the gene expression of dopamine receptor family, COMT, and IL6 to identify novel correlations in BPH and PCa in both blood and tumor of the patients.

Methods: Peripheral blood mononuclear cells from BPH (n= 30) and PCa (n= 30) patients, and prostate tumor tissues (n= 14) along with pathologically normal adjacent tissues (n= 14) were isolated, mRNA was extracted, and cDNA was synthesized, respectively. Quantitative real- time PCR was applied for DRD1- DRD5, COMT, and IL6 genes in all samples.

Results: We found, for the first time, that the expression of COMT and IL6 genes were inversely correlated with the expression of DRD1 and DRD2 genes through the extent of differentiation of PCa from BPH condition. In addition, the PSA levels were correlated with the expression of DRD1 in BPH cases and DRD1, DRD4, DRD5, and IL6 in PCa cases.

Conclusion: Results implicate a potential cross- talk between the signaling pathways derived by IL6 cytokine and dopamine receptors in PCa. Thus, it seems promising to reassemble the consequent signaling pathways by adequate agonists and antagonists to help increase therapeutic efficacy.

Keywords: Prostate cancer, benign prostatic hyperplasia, gene expression analysis, dopamine receptors gene family, IL6 pro-inflammatory cytokine, inflammation.

[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Pakzad R, Rafiemanesh H, Ghoncheh M, et al. Prostate cancer in Iran: Trends in incidence and morphological and epidemiological characteristics. Asian Pac J Cancer Prev 2016; 17(2): 839-43.
[http://dx.doi.org/10.7314/APJCP.2016.17.2.839] [PMID: 26925689]
[3]
Gooren L. Androgen deficiency in the aging male: Benefits and risks of androgen supplementation. J Steroid Biochem Mol Biol 2003; 85(2-5): 349-55.
[http://dx.doi.org/10.1016/S0960-0760(03)00206-1] [PMID: 12943721]
[4]
Miah S, Catto J. BPH and prostate cancer risk.Indian journal of urology: IJU. Journal of the Urological Society of India 2014; 30: 214.
[http://dx.doi.org/10.4103/0970-1591.126909]
[5]
Ullrich PM, Carson MR, Lutgendorf SK, Williams RD. Cancer fear and mood disturbance after radical prostatectomy: Consequences of biochemical evidence of recurrence. J Urol 2003; 169(4): 1449-52.
[http://dx.doi.org/10.1097/01.ju.0000053243.87457.60] [PMID: 12629381]
[6]
Flores IE, Sierra-Fonseca JA, Davalos O, et al. Stress alters the expression of cancer-related genes in the prostate. BMC Cancer 2017; 17(1): 621.
[http://dx.doi.org/10.1186/s12885-017-3635-4] [PMID: 28874141]
[7]
Dronca RS, Markovic SN, Holtan SG, Porrata LF. Neuro-endocrine-immune crosstalk and implications for cancer therapy. J Cell Sci Ther 2011; 2: 102e.
[8]
Jobling P, Pundavela J, Oliveira SM, Roselli S, Walker MM, Hondermarck H. Nerve–cancer cell cross-talk: A novel promoter of tumor progression. Cancer Res 2015; 75(9): 1777-81.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3180] [PMID: 25795709]
[9]
Zhang X, Liu Q, Liao Q, Zhao Y. Potential roles of peripheral dopamine in tumor immunity. J Cancer 2017; 8(15): 2966-73.
[http://dx.doi.org/10.7150/jca.20850] [PMID: 28928888]
[10]
Shalapour S, Karin M. Immunity, inflammation, and cancer: An eternal fight between good and evil. J Clin Invest 2015; 125(9): 3347-55.
[http://dx.doi.org/10.1172/JCI80007] [PMID: 26325032]
[11]
Kuol N, Stojanovska L, Apostolopoulos V, Nurgali K. Crosstalk between cancer and the neuro-immune system. J Neuroimmunol 2018; 315: 15-23.
[http://dx.doi.org/10.1016/j.jneuroim.2017.12.016] [PMID: 29306400]
[12]
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci 2008; 9(1): 46-56.
[http://dx.doi.org/10.1038/nrn2297] [PMID: 18073775]
[13]
Kitagami T, Yamada K, Miura H, Hashimoto R, Nabeshima T, Ohta T. Mechanism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: Role of nitric oxide as a signal crossing the blood-brain barrier. Brain Res 2003; 978(1-2): 104-14.
[http://dx.doi.org/10.1016/S0006-8993(03)02776-8] [PMID: 12834904]
[14]
Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: Psychoneuroimmunology at the translational interface. Brain Behav Immun 2009; 23(2): 149-58.
[http://dx.doi.org/10.1016/j.bbi.2008.08.006] [PMID: 18793712]
[15]
Sarkar C, Chakroborty D, Basu S. Neurotransmitters as regulators of tumor angiogenesis and immunity: The role of catecholamines. J Neuroimmune Pharmacol 2013; 8(1): 7-14.
[http://dx.doi.org/10.1007/s11481-012-9395-7] [PMID: 22886869]
[16]
Chakroborty D, Sarkar C, Mitra RB, Banerjee S, Dasgupta PS, Basu S. Depleted dopamine in gastric cancer tissues: Dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. Clin Cancer Res 2004; 10(13): 4349-56.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0059] [PMID: 15240521]
[17]
Chakroborty D, Chowdhury UR, Sarkar C, Baral R, Dasgupta PS, Basu S. Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization. J Clin Invest 2008; 118(4): 1380-9.
[http://dx.doi.org/10.1172/JCI33125] [PMID: 18340382]
[18]
Beaulieu J-M, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011; 63(1): 182-217.
[http://dx.doi.org/10.1124/pr.110.002642] [PMID: 21303898]
[19]
Beaulieu JM, Espinoza S, Gainetdinov RR. Dopamine receptors - IUPHAR Review 13. Br J Pharmacol 2015; 172(1): 1-23.
[http://dx.doi.org/10.1111/bph.12906] [PMID: 25671228]
[20]
Cherubini E, Di Napoli A, Noto A, et al. Genetic and functional analysis of polymorphisms in the human dopamine receptor and transporter genes in small cell lung cancer. J Cell Physiol 2016; 231(2): 345-56.
[http://dx.doi.org/10.1002/jcp.25079] [PMID: 26081799]
[21]
Mao M, Yu T, Hu J, Hu L. Dopamine D2 receptor blocker thioridazine induces cell death in human uterine cervical carcinoma cell line SiHa. J Obstet Gynaecol Res 2015; 41(8): 1240-5.
[http://dx.doi.org/10.1111/jog.12691] [PMID: 25832589]
[22]
Nikolouzos S, Zacharia G, Mouzakiti A, Kapodistrias N, Douvelis E, et al. Applied evidence-based medicine. Guidelines for the diagnosis and management of lung cancer. Hellenic Journal of Surgery 2015; 87: 441-57.
[http://dx.doi.org/10.1007/s13126-015-0256-8]
[23]
Pornour M, Ahangari G, Hejazi SH, Ahmadkhaniha HR, Akbari ME. Dopamine receptor gene (DRD1-DRD5) expression changes as stress factors associated with breast cancer. Asian Pac J Cancer Prev 2014; 15(23): 10339-43.
[http://dx.doi.org/10.7314/APJCP.2014.15.23.10339] [PMID: 25556472]
[24]
Sarkar C, Chakroborty D, Chowdhury UR, Dasgupta PS, Basu S. Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models. Clin Cancer Res 2008; 14(8): 2502-10.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1778] [PMID: 18413843]
[25]
Andersen S, Skorpen F. Variation in the COMT gene: Implications for pain perception and pain treatment. Pharmacogenomics 2009; 10(4): 669-84.
[http://dx.doi.org/10.2217/pgs.09.13] [PMID: 19374521]
[26]
Kumari N, Dwarakanath BS, Das A, Bhatt AN. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol 2016; 37(9): 11553-72.
[http://dx.doi.org/10.1007/s13277-016-5098-7] [PMID: 27260630]
[27]
Nguyen DP, Li J, Tewari AK. Inflammation and prostate cancer: The role of interleukin 6 (IL-6). BJU Int 2014; 113(6): 986-92.
[http://dx.doi.org/10.1111/bju.12452] [PMID: 24053309]
[28]
Drachenberg DE, Elgamal AAA, Rowbotham R, Peterson M, Murphy GP. Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate 1999; 41(2): 127-33.
[http://dx.doi.org/10.1002/(SICI)1097-0045(19991001)41:2<127:AID-PROS7>3.0.CO;2-H] [PMID: 10477909]
[29]
Culig Z, Bartsch G, Hobisch A. Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Mol Cell Endocrinol 2002; 197(1-2): 231-8.
[http://dx.doi.org/10.1016/S0303-7207(02)00263-0] [PMID: 12431817]
[30]
Engelhardt PF, Seklehner S, Brustmann H, Lusuardi L, Riedl CR. Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: Association with asymptomatic inflammatory prostatitis NIH category IV. Scand J Urol 2015; 49(2): 120-6.
[http://dx.doi.org/10.3109/21681805.2014.971427] [PMID: 25363611]
[31]
Yu S-H, Zheng Q, Esopi D, Macgregor-Das A, Luo J, et al. A paracrine role for IL-6 in prostate cancer patients: Lack of production by primary or metastatic tumor cells Cancer immunology research: Canimm 00132015 2015.
[32]
Culig Z, Puhr M. Interleukin-6 and prostate cancer: Current developments and unsolved questions. Mol Cell Endocrinol 2018; 462(Pt A): 25-30.
[http://dx.doi.org/10.1016/j.mce.2017.03.012] [PMID: 28315704]
[33]
Santer FR, Malinowska K, Culig Z, Cavarretta IT. Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells. Endocr Relat Cancer 2010; 17(1): 241-53.
[http://dx.doi.org/10.1677/ERC-09-0200] [PMID: 19966016]
[34]
Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003; 374(Pt 1): 1-20.
[http://dx.doi.org/10.1042/bj20030407] [PMID: 12773095]
[35]
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017; 45(D1): D353-61.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[36]
Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res 2016; 44(D1): D457-62.
[http://dx.doi.org/10.1093/nar/gkv1070] [PMID: 26476454]
[37]
Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28(1): 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]
[38]
Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37(1): 1-13.
[http://dx.doi.org/10.1093/nar/gkn923] [PMID: 19033363]
[39]
Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[40]
Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, et al. Updates in the eighth edition of the tumor-nodemetastasis staging classification for urologic cancers European urology. 2018; 73: pp. 560-9.
[41]
Kuol N, Stojanovska L, Apostolopoulos V, Nurgali K. Crosstalk between cancer and the neuro-immune system. J Neuroimmunol 2017.
[PMID: 29306400]
[42]
Jope RS, Cheng Y, Lowell JA, Worthen RJ, Sitbon YH, Beurel E. Stressed and inflamed, can GSK3 be blamed? Trends Biochem Sci 2017; 42(3): 180-92.
[http://dx.doi.org/10.1016/j.tibs.2016.10.009] [PMID: 27876551]
[43]
Vignozzi L, Rastrelli G, Corona G, Gacci M, Forti G, Maggi M. Benign prostatic hyperplasia: A new metabolic disease? J Endocrinol Invest 2014; 37(4): 313-22.
[http://dx.doi.org/10.1007/s40618-014-0051-3] [PMID: 24458832]
[44]
La Vignera S, Condorelli RA, Russo GI, Morgia G, Calogero AE. Endocrine control of benign prostatic hyperplasia. Andrology 2016; 4(3): 404-11.
[http://dx.doi.org/10.1111/andr.12186] [PMID: 27089546]
[45]
De Marzo AM, Platz EA, Sutcliffe S, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7(4): 256-69.
[http://dx.doi.org/10.1038/nrc2090] [PMID: 17384581]
[46]
Thapa D, Ghosh R. Chronic inflammatory mediators enhance prostate cancer development and progression. Biochem Pharmacol 2015; 94(2): 53-62.
[http://dx.doi.org/10.1016/j.bcp.2014.12.023] [PMID: 25593038]
[47]
Ou Z, He Y, Qi L, et al. Infiltrating mast cells enhance benign prostatic hyperplasia through IL-6/STAT3/Cyclin D1 signals. Oncotarget 2017; 8(35): 59156-64.
[http://dx.doi.org/10.18632/oncotarget.19465] [PMID: 28938626]
[48]
Miličević N, Mrčela M, Galić J, Marjanović K. Expression of proinflammatory cytokine interleukin-6 in tissue samples of human prostate obtained by needle biopsy. Pathol Res Pract 2015; 211(11): 865-70.
[http://dx.doi.org/10.1016/j.prp.2015.08.008] [PMID: 26376467]
[49]
Albino D, Civenni G, Rossi S, Mitra A, Catapano CV, Carbone GM. The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment. Oncotarget 2016; 7(47): 76756-68.
[http://dx.doi.org/10.18632/oncotarget.12525] [PMID: 27732936]
[50]
Beck GCh, Brinkkoetter P, Hanusch C, et al. Clinical review: Immunomodulatory effects of dopamine in general inflammation. Crit Care 2004; 8(6): 485-91.
[http://dx.doi.org/10.1186/cc2879] [PMID: 15566620]
[51]
Magnon C, Hall SJ, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression. Science 2013; 341(6142)1236361
[http://dx.doi.org/10.1126/science.1236361] [PMID: 23846904]
[52]
Lu D, Carlsson J, Penney KL, et al. Expression and genetic variation in neuroendocrine signaling pathways in lethal and nonlethal prostate cancer among men diagnosed with localized disease. Cancer Epidemiol Biomarkers Prev 2017; 26(12): 1781-7.
[http://dx.doi.org/10.1158/1055-9965.EPI-17-0453] [PMID: 28939587]
[53]
Hayakawa Y, Wang TC. Nerves switch on angiogenic metabolism. Science 2017; 358(6361): 305-6.
[http://dx.doi.org/10.1126/science.aaq0365] [PMID: 29051365]
[54]
Lang K, Drell TL IV, Lindecke A, et al. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer 2004; 112(2): 231-8.
[http://dx.doi.org/10.1002/ijc.20410] [PMID: 15352035]
[55]
Moreno-Smith M, Lu C, Shahzad MM, et al. Dopamine blocks stress-mediated ovarian carcinoma growth. Clin Cancer Res 2011; 17(11): 3649-59.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2441] [PMID: 21531818]
[56]
Chakroborty D, Sarkar C, Mitra RB, Banerjee S, Dasgupta PS, Basu S. Depleted dopamine in gastric cancer tissues: Dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. Clin Cancer Res 2004; 10(13): 4349-56.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0059] [PMID: 15240521]
[57]
Huang H, Wu K, Ma J, Du Y, Cao C, Nie Y. Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway. Int Immunopharmacol 2016; 39: 113-20.
[http://dx.doi.org/10.1016/j.intimp.2016.07.002] [PMID: 27468100]
[58]
Shaikhpoor M, Ahangari G, Sadeghizadeh M, Khosravi A, Derakhshani Deilami G. Significant changes in D2-like dopamine gene receptors expression associated with non-small-cell lung cancer: Could it be of potential use in the design of future therapeutic strategies? Curr Cancer Ther Rev 2012; 8: 304-10.
[59]
Borcherding DC, Tong W, Hugo ER, et al. Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer. Oncogene 2016; 35(24): 3103-13.
[http://dx.doi.org/10.1038/onc.2015.369] [PMID: 26477316]
[60]
Pornour M, Ahangari G, Hejazi SH, Deezagi A. New perspective therapy of breast cancer based on selective dopamine receptor D2 agonist and antagonist effects on MCF-7 cell line. Recent Patents Anticancer Drug Discov 2015; 10(2): 214-23.
[http://dx.doi.org/10.2174/1574892810666150416111831] [PMID: 25876608]
[61]
Ahangari G, Pornour M, Aminzadeh S, Bakhtou H, Ahmadkhaniha H. Significant association between catechol amine o-methyl transferase (COMT) gene expression changes and breast cancer pathogenesis. J Carcinog Mutagen 2015; 6: 2.
[62]
Wen W, Ren Z, Shu XO, et al. Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer risk. Cancer Epidemiol Biomarkers Prev 2007; 16(5): 917-20.
[http://dx.doi.org/10.1158/1055-9965.EPI-06-1032] [PMID: 17507616]
[63]
Parrado AC, Canellada A, Gentile T, Rey-Roldán EB. Dopamine agonists upregulate IL-6 and IL-8 production in human keratinocytes. Neuroimmunomodulation 2012; 19(6): 359-66.
[http://dx.doi.org/10.1159/000342140] [PMID: 23051896]
[64]
Borcherding DC, Hugo ER, Idelman G, et al. Dopamine receptors in human adipocytes: Expression and functions. PLoS One 2011; 6(9)e25537
[http://dx.doi.org/10.1371/journal.pone.0025537] [PMID: 21966540]
[65]
Capellino S, Cosentino M, Luini A, et al. Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: Inhibitory effects of dopamine on interleukin-8 and interleukin-6. Arthritis Rheumatol 2014; 66(10): 2685-93.
[http://dx.doi.org/10.1002/art.38746] [PMID: 24965369]
[66]
Lan Y-L, Wang X, Xing J-S, et al. Anti-cancer effects of dopamine in human glioma: Involvement of mitochondrial apoptotic and anti-inflammatory pathways. Oncotarget 2017; 8(51): 88488-500.
[http://dx.doi.org/10.18632/oncotarget.19691] [PMID: 29179451]
[67]
Zhang Y, Jiang X, Qin C, Cuevas S, Jose PA, Armando I. Dopamine D2 receptors’ effects on renal inflammation are mediated by regulation of PP2A function. Am J Physiol Renal Physiol 2016; 310(2): F128-34.
[http://dx.doi.org/10.1152/ajprenal.00453.2014] [PMID: 26290374]
[68]
Mladenović A, Perović M, Raicević N, Kanazir S, Rakić L, Ruzdijić S. 6-Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats. Brain Res 2004; 996(2): 237-45.
[http://dx.doi.org/10.1016/j.brainres.2003.10.035] [PMID: 14697501]
[69]
Colombo C, Cosentino M, Marino F, et al. Dopaminergic modulation of apoptosis in human peripheral blood mononuclear cells: Possible relevance for Parkinson’s disease. Ann N Y Acad Sci 2003; 1010: 679-82.
[http://dx.doi.org/10.1196/annals.1299.124] [PMID: 15033811]
[70]
Chappell WH, Abrams SL, Lertpiriyapong K, et al. Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells. Adv Biol Regul 2016; 60: 64-87.
[http://dx.doi.org/10.1016/j.jbior.2015.10.001] [PMID: 26525204]
[71]
Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1999; 401(6748): 82-5.
[http://dx.doi.org/10.1038/43466] [PMID: 10485710]
[72]
Atretkhany KN, Drutskaya MS, Nedospasov SA, Grivennikov SI, Kuprash DV. Chemokines, cytokines and exosomes help tumors to shape inflammatory microenvironment. Pharmacol Ther 2016; 168: 98-112.
[http://dx.doi.org/10.1016/j.pharmthera.2016.09.011] [PMID: 27613100]
[73]
Attard G, Parker C, Eeles RA, et al. Prostate cancer. Lancet 2016; 387(10013): 70-82.
[http://dx.doi.org/10.1016/S0140-6736(14)61947-4] [PMID: 26074382]
[74]
Mazzucchelli R, Colanzi P, Pomante R, Muzzonigro G, Montironi R. Prostate tissue and serum markers Advances in clinical pathology: The official journal of Adriatic Society of Pathology 2000 ; 4: 111-20.
[75]
Colombatti M, Grasso S, Porzia A, et al. The prostate specific membrane antigen regulates the expression of IL-6 and CCL5 in prostate tumour cells by activating the MAPK pathways. PLoS One 2009; 4(2)E4608
[http://dx.doi.org/10.1371/journal.pone.0004608] [PMID: 19242540]


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VOLUME: 19
ISSUE: 8
Year: 2019
Page: [605 - 619]
Pages: 15
DOI: 10.2174/1566524019666190709180146
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