title: Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma.
abstract: In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bednarek
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kiwerska
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Szaumkessel
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kostrzewska-Poczekaj
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.|Department of Oncologic Pathology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Marszalek
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Janiszewska
authors.affiliation: Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bartochowska
authors.affiliation: Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jackowska
authors.affiliation: Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Wierzbicka
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery and Department of Medical Biochemistry, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Grenman
authors.affiliation: Department of Audiology and Phoniatry, University of Medical Sciences, Poznan, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Szyfter
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland.|Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Giefing
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. maljar@man.poznan.pl.|Department of Hematology, University of Medical Sciences, Poznan, Poland. maljar@man.poznan.pl.
authors.forename: M
authors.initials: M
authors.lastname: Jarmuz-Szymczak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: CDK1; Gene methylation; Immunohistochemistry; Overexpression; Western blot; microRNA