title: Genetic and functional analyses do not explain the association of high PRC1 expression with poor survival of breast carcinoma patients.
abstract: Microtubules are vitally important for eukaryotic cell division. Therefore, we evaluated the relevance of mitotic kinesin KIF14, protein-regulating cytokinesis 1 (PRC1), and citron kinase (CIT) for the prognosis of breast carcinoma patients. Transcript levels were assessed by quantitative real-time PCR in tissues from two independent groups of breast carcinoma patients and compared with clinical data. Tissue PRC1 protein levels were estimated using immunoblotting, and the PRC1 tagged haplotype was analyzed in genomic DNA. A functional study was performed in MDA-MB-231 cells in vitro. KIF14, PRC1, and CIT transcripts were overexpressed in tumors compared with control tissues. Tumors without expression of hormonal receptors or high-grade tumors expressed significantly higher KIF14 and PRC1 levels than hormonally-positive or low-grade tumors. Patients with high intra-tumoral PRC1 levels had significantly worse disease-free survival than patients with low levels. PRC1 rs10520699 and rs11852999 polymorphisms were associated with PRC1 transcript levels, but not with patientś survival. Paclitaxel-induced PRC1 expression, but PRC1 knockdown did not modify the paclitaxel cytotoxicity in vitro. PRC1 overexpression predicts poor disease-free survival of patients with breast carcinomas. Genetic variability of PRC1 and the protein interaction with paclitaxel cytotoxicity do not explain this association.
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic.
authors: Veronika
authors: V
authors: Brynychova
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic.
authors: Marie
authors: M
authors: Ehrlichova
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic.
authors: Viktor
authors: V
authors: Hlavac
authors: Division of Cell & Molecular Biology, 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors: Vlasta
authors: V
authors: Nemcova-Furstova
authors: Institute for the Care for Mother and Child, Prague, Czech Republic.
authors: Vaclav
authors: V
authors: Pecha
authors: Institute for the Care for Mother and Child, Prague, Czech Republic.
authors: Jelena
authors: J
authors: Leva
authors: Biolab Praha, k.s., Prague, Czech Republic.
authors: Marketa
authors: M
authors: Trnkova
authors: Department of Pathology and Molecular Medicine, Motol University Hospital, Prague, Czech Republic.
authors: Marcela
authors: M
authors: Mrhalova
authors: Department of Pathology and Molecular Medicine, Motol University Hospital, Prague, Czech Republic.
authors: Roman
authors: R
authors: Kodet
authors: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors: David
authors: D
authors: Vrana
authors: Division of Cell & Molecular Biology, 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors: Jan
authors: J
authors: Kovar
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
authors: Radka
authors: R
authors: Vaclavikova
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
authors: Ivan
authors: I
authors: Gut
authors: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic. Electronic address: pavel.soucek@szu.cz.
authors: Pavel
authors: P
authors: Soucek
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D017239:Paclitaxel / Q000494:pharmacology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C116662:PRC1 protein, human; D012333:RNA, Messenger; D017239:Paclitaxel
keywords: Breast carcinoma; Cytokinesis; Expression; Genetic; Marker