title: ING3 is associated with increased cell invasion and lethal outcome in ERG-negative prostate cancer patients.
abstract: The inhibitor of growth family member 3 (ING3) is a member of the ING tumor suppressor family. Although its expression has been reported in various types of cancers, the role of ING3 and its prognostic value in prostate cancer (PCa) has not been investigated. ING3 expression and prognostic value was assessed in a cohort of PCa patients (n = 312) treated with transurethral resection of prostate using immumoflourescent automated quantitative analysis (AQUA) system. In vitro studies were carried out in conjunction to investigate its expression in various PCa cell lines. ING3 knockdown was also carried out in DU145 cell lines to assess for any changes in invasion and migration. ING3 expression was highest in benign prostate tissues (mean 3.2 ± 0.54) compared to PCa (mean 2.5 ± 0.26) (p = 0.437), advanced prostate cancer (AdvPCa) (mean 1.5 ± 0.32) (p = 0.004), and castration-resistant prostate cancer (CRPC) (mean 2.28 ± 0.32) (p = 0.285). ING3 expression was inversely correlated to Gleason score (p = 0.039) and ETS-related gene (ERG) expression (p = 0.019). Higher ING3 expression was marginally associated with lethal disease (p = 0.052), and this was more pronounced in patients with ERG-negative status (p = 0.018). Inhibition of ING3 in DU145 PCa cells using small interfering RNA (siRNA) was associated with decreased cell invasion (p = 0.0016) and cell migration compared to control cells. ING3 is significantly associated with PCa disease progression and cancer-specific mortality. To our knowledge, this is the first report suggesting an oncogenic function of ING3, previously well known as a tumor suppressor protein. Further studies should investigate potential-related pathways in association to ING3.
authors.affiliation: Medical Science Department Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.|Arnie Charbonneau Cancer Institute and Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Amal
authors.initials: A
authors.lastname: Almami
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Samar A
authors.initials: SA
authors.lastname: Hegazy
authors.affiliation: Medical Science Department Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.|Arnie Charbonneau Cancer Institute and Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Nabbi
authors.affiliation: The Prostate Centre, Calgary, Alberta, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Asma
authors.initials: A
authors.lastname: Salman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Hatem
authors.initials: H
authors.lastname: Abou-Ouf
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.|Departments of Oncology, Biochemistry and Molecular Biology, Calgary, Alberta, Canada.|Arnie Charbonneau Cancer Institute and Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Karl
authors.initials: K
authors.lastname: Riabowol
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada. tarek.bismar@cls.ab.ca.|Departments of Oncology, Biochemistry and Molecular Biology, Calgary, Alberta, Canada. tarek.bismar@cls.ab.ca.|Arnie Charbonneau Cancer Institute and Tom Baker Cancer Center, Calgary, Alberta, Canada. tarek.bismar@cls.ab.ca.|The Prostate Centre, Calgary, Alberta, Canada. tarek.bismar@cls.ab.ca.|Departments of Pathology & Laboratory Medicine and Oncology, University of Calgary-Cumming School of Medicine, Rockyview General Hospital, Calgary, Alberta, T2V 1P9, Canada. tarek.bismar@cls.ab.ca.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Bismar
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000071230:Transcriptional Regulator ERG / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; C072312:ERG protein, human; D018398:Homeodomain Proteins; C459806:ING3 protein, human; D012333:RNA, Messenger; D011944:Receptors, Androgen; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins
keywords: ING3; Invasion; Metastasis; Oncogene; Progression; Prostate cancer; Tumor suppressor