title: KCTD11 tumor suppressor gene expression is reduced in prostate adenocarcinoma.
abstract: Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN) is a tumor suppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and in several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling. Here, we demonstrated that KCTD11 LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog pathway. Low levels of KCTD11 mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led to growth arrest. Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic markers.
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zazzeroni
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nicosia
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessitore
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Gallo
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Verzella
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Mariafausta
authors.initials: M
authors.lastname: Fischietti
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vecchiotti
authors.affiliation: Department of Pathology, San Salvatore Hospital, 67100 L'Aquila, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ventura
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Capece
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Via Regina Elena 291, 00161 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D014166:Transferases
chemical_list: D018797:Cell Cycle Proteins; D015221:Potassium Channels; C488725:KCTD11 protein, human; D014166:Transferases