title: 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression.
abstract: Previously we identified and deorphaned G-protein-coupled receptor 31 (GPR31) as the high-affinity 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptor (12-HETER1). Here we have determined its distribution in prostate cancer tissue and its role in prostate tumorigenesis using in vitro and in vivo assays. Data-mining studies strongly suggest that 12-HETER1 expression positively correlates with the aggressiveness and progression of prostate tumors. This was corroborated with real-time PCR analysis of human prostate tumor tissue arrays that revealed the expression of 12-HETER1 positively correlates with the clinical stages of prostate cancers and Gleason scores. Immunohistochemistry analysis also proved that the expression of 12-HETER1 is positively correlated with the grades of prostate cancer. Knockdown of 12-HETER1 in prostate cancer cells markedly reduced colony formation and inhibited tumor growth in animals. To discover the regulatory factors, 5 candidate 12-HETER1 promoter cis elements were assayed as luciferase reporter fusions in Chinese hamster ovary (CHO) cells, where the putative cis element required for gene regulation was mapped 2 kb upstream of the 12-HETER1 transcriptional start site. The data implicate 12-HETER1 in a critical new role in the regulation of prostate cancer progression and offer a novel alternative target for therapeutic intervention.-Honn, K. V., Guo, Y., Cai, Y., Lee, M.-J., Dyson, G., Zhang, W., Tucker, S. C. 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression.
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA; Department of Chemistry, Wayne State University, Detroit, Michigan, USA Department of Oncology, School of Medicine, Wayne State University, Detroit, Michigan, USA;
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Honn
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA;
authors.forename: Yande
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA;
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA;
authors.forename: Menq-Jer
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Oncology, School of Medicine, Wayne State University, Detroit, Michigan, USA; Biostatics Core, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dyson
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA;
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA; stucker@med.wayne.edu.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tucker
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D019295:Computational Biology; D006224:Cricetinae; D016208:Databases, Factual; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D059467:Transcriptome; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C066652:12-hydroxyeicosatetraenoic acid receptor; C501953:GPR31 protein, human; D018055:Receptors, Eicosanoid; D043562:Receptors, G-Protein-Coupled
keywords: 12(S)-HETE; arachidonate metabolism in malignancy; inflammatory pathway