RESUMO
BACKGROUND: Striking similarities between stem cells and cancer cells have led to the concept of the existence of a cancer stem cell, a concept that has since been documented in many tumours including breast, brain and prostate tumours. Teratocarcinomas are malignant tumours occurring predominantly in the testes composed of undifferentiated stem cells and mature tissues. Cancer stemness was studied using the teratocarcinoma model of tumourigenesis. MATERIALS AND METHODS: The gene expression profile of murine embryonic stem cell lines was compared to its malignant counterpart, murine teratocarcinoma cell lines. Validation was performed using real-time quantitative PCR. RESULTS: A list of 1170 differentially expressed genes was obtained. Significant pathways involved in cancer stemness included oxidative stress and angiogenesis. Transcription factors and extracellular matrix molecules appeared prominently. CONCLUSION: Novel molecules have been highlighted including decorin, an extracellular matrix protein, which may provide opportunities for the investigation of innovative strategies in the future treatment of cancer.
Assuntos
Células-Tronco Neoplásicas/química , RNA Mensageiro/análise , Teratocarcinoma/genética , Animais , Linhagem Celular Tumoral , Células-Tronco de Carcinoma Embrionário , Células-Tronco Embrionárias/patologia , Células-Tronco Embrionárias/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Camundongos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Teratocarcinoma/química , Teratocarcinoma/patologia , Transcrição GênicaRESUMO
BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29-69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis. AIM: The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis. RESULTS: A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets.
Assuntos
Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica , Modelos Biológicos , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Transcrição Gênica , Adulto , Análise por Conglomerados , Perfilação da Expressão Gênica , Glutamina/genética , Humanos , MicroRNAs/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Valina/genéticaRESUMO
BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. AIM: The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. RESULTS: DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement.Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis.