RESUMO
BACKGROUND: Cancer development involves an "injury" to the respiratory machinery (Warburg effect) due to decreased or impaired mitochondrial function. This circumstance results in a down regulation of some of the ATPase subunits of the malignant tissue. The objective of this work was to assess and compare the relative expression of mRNA of mitochondrial ATPase subunits between samples of thyroid cancer and benign nodules. MATERIAL AND METHODS: Samples from 31 patients who had an operation for PTC at the General Hospital of Mexico were snap-frozen and stored at -70°C. Thirty-five patients who had an operation for benign tumors were also included in the study. mRNA expression levels of alpha, beta, gamma, and epsilon subunits of F1 and "c12" of subunit Fo were determined by real-time RT-PCR (by duplicate), in order to determine if abnormal expression of these genes could partially explain the Warburg effect in papillary thyroid cancer (PTC). RESULTS: ATP5E transcript alteration (down-expression) was highly associated to PTC diagnosis OR=11.76 (95% confidence interval, 1.245-237.98; p=0.04). CONCLUSIONS: Relative down-expression of ATP5E transcript was highly associated with PTC diagnosis. This transcript alteration may be used as a tumoral marker in papillary thyroid cancer.
Assuntos
Carcinoma/enzimologia , Carcinoma/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Proteínas/genética , RNA Mensageiro/genética , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma/patologia , Carcinoma Papilar , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , ATPases Mitocondriais Próton-Translocadoras/biossíntese , Estudos Prospectivos , Proteínas/metabolismo , RNA Mensageiro/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem , Proteína Inibidora de ATPaseRESUMO
Mitochondria play an important role during sporogenesis in plants. The steady state levels of the nuclear-encoded mitochondrial complex I (nCI), PSST, TYKY and NADHBP transcripts increase in flowers of male-sterile plants with impairment of mitochondrial function generated by the expression of the unedited version of ATP9 (u-ATP9). This suggests a nuclear control of nCI genes in response to the mitochondrial flaw. To evaluate this hypothesis, transgenic plants carrying the GUS reporter gene, under the control of the PSST, TYKY and NADHBP promoters, were constructed. We present evidence that suppression by antisense strategy of the expression of u-ATP9 restores the normal levels of three nCI transcripts, indicating that the increase in PSST, TYKY and NADHBP in plants with a mitochondrial flaw occurs at the transcriptional level. The data presented here support the hypothesis that a mitochondrial dysfunction triggers a retrograde signaling which induce some nuclear-encoded mitochondrial genes. Moreover, these results demonstrate that this is a valuable experimental model for studying nucleus-mitochondria cross-talk events.
Assuntos
Proteínas de Arabidopsis/antagonistas & inibidores , Arabidopsis/fisiologia , Complexo I de Transporte de Elétrons/biossíntese , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , Transgenes/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/biossíntese , Proteínas de Arabidopsis/genética , Complexo I de Transporte de Elétrons/genética , Fertilidade , Genes Reporter , Germinação , ATPases Mitocondriais Próton-Translocadoras/biossíntese , ATPases Mitocondriais Próton-Translocadoras/genética , Plantas Geneticamente Modificadas , Pólen/fisiologia , Regiões Promotoras Genéticas , Transdução de Sinais , Ativação Transcricional , Transgenes/genéticaRESUMO
To study the effect of a mitochondrial dysfunction induced by the expression of the unedited form of the subunit 9 of ATP synthase gene (u-atp9) in Arabidopsis, we constructed transgenic plants expressing u-atp9 under the control of three different promoters: CaMV 35S, apetala 3 and A9. The size and shape of transgenic plants bearing the apetala3::u-atp9 and A9::u-atp9 genes looked normal while the 35S::u-atp9 transformed plants showed a dwarf morphology. All u-atp9 expressing plants, independent of the promoter used, exhibited a male sterile phenotype. Molecular analysis of male sterile plants revealed the induction of the mitochondrial nuclear complex I (nCI) genes, psst, tyky and nadh binding protein (nadhbp), associated with a mitochondrial dysfunction. These results support the hypothesis that the expression of u-atp9 can induce male sterility and reveal that the apetala3::u-atp9 and A9::u-atp9 plants induced the sterile phenotype without affecting the vegetative development of Arabidopsis plants. Moreover, male sterile plants produced by this procedure are an interesting model to study the global changes generated by an engineered mitochondrial dysfunction at the transcriptome and proteome levels in Arabidopsis plants.