Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas
| Autor: | Arvind Y. M. Sundaram, Camilla Maria Falch, Kjersti Ringvoll Normann, Marianne Andersen, Ivars Silamikelis, Tove Lekva, Nicoleta Cristina Olarescu, Jens Bollerslev, Kristin Astrid Berland Øystese, Alexander Eieland |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Receptors Cell Surface/genetics 0301 basic medicine Time Factors Endocrinology Diabetes and Metabolism RNA Messenger/metabolism Adaptor Proteins Signal Transducing/genetics Endocrinology Cell Movement Gene expression Nerve Tissue Proteins/genetics Myosin Type I/genetics Regulation of gene expression Membrane Glycoproteins Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins RNA-Binding Proteins Follicle Stimulating Hormone/metabolism MTDH General Medicine Middle Aged Cadherins Gene Expression Regulation Neoplastic Female Luteinizing Hormone/metabolism Cell Adhesion Molecules/genetics Microtubule-Associated Proteins Adenoma Adult medicine.medical_specialty Epithelial-Mesenchymal Transition Sialoglycoproteins Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/genetics Nerve Tissue Proteins Receptors Cell Surface In Vitro Techniques Biology Ribonucleases/genetics Sialoglycoproteins/genetics Myosin Type I 03 medical and health sciences Ribonucleases Downregulation and upregulation Epithelial-Mesenchymal Transition/genetics Proto-Oncogene Proteins Internal medicine Cell Movement/genetics medicine Humans Gene silencing Pituitary Neoplasms RNA Messenger Gene Silencing Gene Adaptor Proteins Signal Transducing Aged Cyclic AMP-Dependent Protein Kinase Catalytic Subunits Cadherins/genetics Gene Expression Profiling Membrane Proteins Luteinizing Hormone Membrane Glycoproteins/genetics Microtubule-Associated Proteins/genetics medicine.disease Adenoma/genetics Pituitary Neoplasms/genetics Protocadherins Gene expression profiling Proto-Oncogene Proteins/genetics 030104 developmental biology Cancer research Follicle Stimulating Hormone Intracellular Signaling Peptides and Proteins/genetics Cell Adhesion Molecules |
| Zdroj: | Falch, C M, Sundaram, A Y M, Øystese, K A, Normann, K R, Lekva, T, Silamikelis, I, Eieland, A K, Andersen, M S, Bollerslev, J & Olarescu, N C 2018, ' Gene expression profiling of fast-and slow-growing non-functioning gonadotroph pituitary adenomas ', European Journal of Endocrinology, vol. 178, no. 3, pp. 295-307 . https://doi.org/10.1530/EJE-17-0702 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje-17-0702 |
| Popis: | ObjectiveReliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT).Design and methodsEight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencingMTDH(metadherin) andEMCN(endomucin) onin vitromigration of human adenoma cells was evaluated.Results350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group,P-adjusted RP PCDH18, UNC5D, EMCN, MYO1B, GPM6Aand six EMT-related genes (SPAG9, SKIL, MTDH, HOOK1, CNOT6LandPRKACB).MTDH, but notEMCN, demonstrated involvement in cell migration and association with EMT markers.ConclusionsFast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition toMTDH, identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy. |
| Databáze: | OpenAIRE |
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