title: GRM1 is An Androgen-Regulated Gene and its Expression Correlates with Prostate Cancer Progression in Pre-Clinical Models.
abstract: OBJECTIVE
  We recently demonstrated that glutamate receptor GRM1 was expressed at high levels in castration-resistant prostate cancer (CR-PCa) tissues and cells. Herein, we determined the relationship between GRM1 and AR, PSA, and tumor growth, remission, and recurrence in preclinical PCa models. The effect of alterations in GRM1 expression was also investigated on PCa cell growth, migration and invasion.
  
  
  METHODS
  We used quantitative gene expression and immunohistochemistry to define the temporal association between GRM1 expression and AR, PSA, and tumor growth during CR progression in CWR22 (n = 59) and LuCaP 35 (n = 12) PCa xenografts. The effect of alterations in GRM1 expression levels on growth, migration, and invasion was investigated in GRM1-overexpressed or -silenced PCa cell lines. The effect of DHT on GRM1 expression was determined in the presence or absence of the antiandrogen bicalutamide.
  
  
  RESULTS
  We found that GRM1 transcript and tissue expression directly correlated with growth and AR and PSA expression in hormone-sensitive (HS), castrated, and CR tumor xenografts. GRM1 overexpression or silencing directly correlated with PCa cell proliferation, migration, and invasion. DHT increased GRM1 expression via an AR-dependent manner in HS- and CR-PCa cell lines.
  
  
  CONCLUSIONS
  This is a first report of GRM1 as an androgen and AR-target gene. GRM1 expression directly correlated with tumor growth, regression, and recurrence and may contribute to CR-progression of PCa in preclinical models. Further studies are needed to define the utility of GRM1 as a druggable target or biomarker for PCa.
authors.affiliation: Cancer Genetics, Roswell Park Cancer Institute.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Shourideh
authors.affiliation: Pathology, Roswell Park Cancer Institute.
authors.forename: Gissou
authors.initials: G
authors.lastname: Azabdaftari
authors.affiliation: Biostatistics, Roswell Park Cancer Institute.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Attwood
authors.affiliation: Cancer Genetics, Roswell Park Cancer Institute.
authors.forename: Adam
authors.initials: A
authors.lastname: DePriest
authors.affiliation: Cancer Genetics, Roswell Park Cancer Institute.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Wadosky
authors.affiliation: Pharmacology & Therapeutics, Roswell Park Cancer Institute.
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Gillard
authors.affiliation: Pharmacology and Therapeutics, Roswell Park Cancer Institute.
authors.forename: Ellen
authors.initials: E
authors.lastname: Karasik
authors.affiliation: Cancer Biology, Cleveland Clinic.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Heemers
authors.affiliation: Urology, University of Kentucky.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
authors.affiliation: Cancer Genetics, Roswell Park Cancer Institute.
authors.forename: Irwin H
authors.initials: IH
authors.lastname: Gelman
authors.affiliation: Department of Urology, University of Washington.
authors.forename: Eva
authors.initials: E
authors.lastname: Corey
authors.affiliation: Urology, University of Washington.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.affiliation: Urology, Roswell Park Cancer Institute.
authors.forename: James L
authors.initials: JL
authors.lastname: Mohler
authors.affiliation: Cancer Genetics and Urology, Roswell Park Cancer Institute Shahriar.Koochekpour@RoswellPark.org.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Koochekpour