PMID- 26912061 OWN - NLM STAT- MEDLINE DCOM- 20170208 LR - 20200306 IS - 1423-0380 (Electronic) IS - 1010-4283 (Print) IS - 1010-4283 (Linking) VI - 37 IP - 8 DP - 2016 Aug TI - Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma. PG - 11115-26 LID - 10.1007/s13277-016-4991-4 [doi] AB - 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. FAU - Bednarek, K AU - Bednarek K AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. FAU - Kiwerska, K AU - Kiwerska K AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. FAU - Szaumkessel, M AU - Szaumkessel M AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. FAU - Bodnar, M AU - Bodnar M AD - Department of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. FAU - Kostrzewska-Poczekaj, M AU - Kostrzewska-Poczekaj M AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. FAU - Marszalek, A AU - Marszalek A AD - Department of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. AD - Department of Oncologic Pathology, Greater Poland Cancer Centre, Poznan, Poland. FAU - Janiszewska, J AU - Janiszewska J AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. FAU - Bartochowska, A AU - Bartochowska A AD - Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland. FAU - Jackowska, J AU - Jackowska J AD - Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland. FAU - Wierzbicka, M AU - Wierzbicka M AD - Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland. FAU - Grenman, R AU - Grenman R AD - Department of Otorhinolaryngology-Head and Neck Surgery and Department of Medical Biochemistry, Turku University Hospital and University of Turku, Turku, Finland. FAU - Szyfter, K AU - Szyfter K AD - Department of Audiology and Phoniatry, University of Medical Sciences, Poznan, Poland. FAU - Giefing, M AU - Giefing M AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. AD - Department of Otolaryngology and Laryngological Oncology, University of Medical Sciences, Poznan, Poland. FAU - Jarmuz-Szymczak, M AU - Jarmuz-Szymczak M AD - Department of Cancer Genetics, Institute of Human Genetics, PAS, Poznan, Poland. maljar@man.poznan.pl. AD - Department of Hematology, University of Medical Sciences, Poznan, Poland. maljar@man.poznan.pl. LA - eng PT - Journal Article DEP - 20160224 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.11.22 (CDC2 Protein Kinase) RN - EC 2.7.11.22 (CDK1 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis/genetics MH - Blotting, Western MH - CDC2 Protein Kinase MH - Carcinoma, Squamous Cell/*genetics/pathology MH - Cell Line, Tumor MH - Cyclin-Dependent Kinases/analysis/*biosynthesis MH - Female MH - Head and Neck Neoplasms/*genetics/pathology MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*genetics/pathology MH - Oligonucleotide Array Sequence Analysis MH - Polymerase Chain Reaction MH - Squamous Cell Carcinoma of Head and Neck MH - Transcriptome MH - Up-Regulation PMC - PMC4999469 OTO - NOTNLM OT - CDK1 OT - Gene methylation OT - Immunohistochemistry OT - Overexpression OT - Western blot OT - microRNA COIS- Compliance with ethical standards Ethical standards We declare that all experiments were performed in accordance with the current law of Poland. The study was approved by the local ethical board of Medical University in Poznan. Conflicts of interest None. EDAT- 2016/02/26 06:00 MHDA- 2017/02/09 06:00 PMCR- 2016/02/24 CRDT- 2016/02/26 06:00 PHST- 2015/10/29 00:00 [received] PHST- 2016/02/11 00:00 [accepted] PHST- 2016/02/26 06:00 [entrez] PHST- 2016/02/26 06:00 [pubmed] PHST- 2017/02/09 06:00 [medline] PHST- 2016/02/24 00:00 [pmc-release] AID - 10.1007/s13277-016-4991-4 [pii] AID - 4991 [pii] AID - 10.1007/s13277-016-4991-4 [doi] PST - ppublish SO - Tumour Biol. 2016 Aug;37(8):11115-26. doi: 10.1007/s13277-016-4991-4. Epub 2016 Feb 24.