2. Academic Validation
  3. 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

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

  • FASEB J. 2016 Jun;30(6):2360-9. doi: 10.1096/fj.201500076.
Kenneth V Honn 1,  Yande Guo 2,  Yinlong Cai 2,  Menq-Jer Lee 2,  Gregory Dyson 3,  Wenliang Zhang 2,  Stephanie C Tucker 4
Affiliations

Affiliations

  • 1 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;
  • 2 Department of Pathology, Wayne State University, Detroit, Michigan, USA;
  • 3 Department of Oncology, School of Medicine, Wayne State University, Detroit, Michigan, USA; Biostatics Core, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
  • 4 Department of Pathology, Wayne State University, Detroit, Michigan, USA; [email protected].
PMID: 26965684 DOI: 10.1096/fj.201500076
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.

Keywords

12(S)-HETE; arachidonate metabolism in malignancy; inflammatory pathway.

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