This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Interleukin-17 (IL-17) cytokine is increased in 58% of prostate cancer specimens. IL-17A and IL-17F bind to two receptors IL-17RA and IL-17RC. IL-17RA is expressed in both prostatic stromal and epithelial cells, whereas IL-17RC is mainly expressed in the epithelium. IL-17RC has over 13 alternative splice isoforms. Our general hypothesis is that up-regulation of the full-length unglycosylated IL-17RC in prostatic epithelium under chronic inflammation enhances the response of cells to IL-17A and IL-17F cytokines, leading to activation of NF-?B, Akt and ERK pathways that promotes cell proliferation and survival. The long-term objectives are to delineate the mechanisms of how inflammatory cytokines contribute to prostate cancer initiation through their receptors and downstream signaling pathways and to develop anti-inflammatory interventions to prevent and treat prostate cancer.
Three Specific Aims are proposed.
Aim 1 is to identify the shift of balance of IL-17RC isoforms in normal, prostatic intraepithelial neoplasia (PIN) and cancer cells. Our hypothesis is that the full-length unglycosylated IL-17RC is up-regulated in PIN and cancer cells. Human prostate cell lines and tissues representing normal, PIN and cancer will be studied for IL-17RC mRNA isoforms, protein levels and protein glycosylation.
Aim 2 is to identify the mechanisms underlying the functionality of different IL-17RC isoforms. Our hypothesis is that the full-length unglycosylated IL-17RC protein binds to IL-17A and IL-17F cytokines, whereas the exon-deleted and/or glycosylated IL-17RC proteins do not bind to ligands. The ligand-receptor interaction activates downstream NF-?B, Akt and ERK signaling pathways that promote cell proliferation and survival.
Aim 3 is to test the role of IL-17RC in initiation of prostate cancer in vivo using a mouse model with IL-17RC knockout and prostate-specific conditional Pten knockout background. Our hypothesis is that the spontaneous prostate cancer formation in the conditional Pten knockout mice will be prevented or delayed when IL-17RC expression is absent.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-B (01))
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Tulane University
Public Health & Prev Medicine
Schools of Public Health
New Orleans
United States
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Wu, Victor J; Pang, Darren; Tang, Wendell W et al. (2017) Obesity, age, ethnicity, and clinical features of prostate cancer patients. Am J Clin Exp Urol 5:1-9
Zhang, Q; Liu, S; Parajuli, K R et al. (2017) Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene 36:687-699
Gopalakrishnan, Anusha M; Aly, Ahmed S I; Aravind, L et al. (2017) Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response. MBio 8:
Liu, Yao-Zhong; Zhang, Lei; Roy-Engel, Astrid M et al. (2017) Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells. Gene 602:16-23
Yang, Lingyun; Huang, Feng; Mei, Jiandong et al. (2017) Posttranscriptional Control of PD-L1 Expression by 17?-Estradiol via PI3K/Akt Signaling Pathway in ER?-Positive Cancer Cell Lines. Int J Gynecol Cancer 27:196-205
Wang, Xun; Yang, Lingyun; Huang, Feng et al. (2017) Inflammatory cytokines IL-17 and TNF-? up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunol Lett 184:7-14
Ma, Lin; Li, Jingwu; Nie, Qiang et al. (2017) Organoid culture of human prostate cancer cell lines LNCaP and C4-2B. Am J Clin Exp Urol 5:25-33
Servant, Geraldine; Streva, Vincent A; Derbes, Rebecca S et al. (2017) The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition. Genetics 205:139-153
Martin, Elizabeth C; Conger, Adrienne K; Yan, Thomas J et al. (2017) MicroRNA-335-5p and -3p synergize to inhibit estrogen receptor alpha expression and promote tamoxifen resistance. FEBS Lett 591:382-392
Zhang, Qiuyang; Liu, Sen; Ge, Dongxia et al. (2017) Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model. Prostate 77:888-899

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