RESUMO
The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/genética , Neoplasias Colorretais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Regulação para Baixo/genética , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Regulação para Cima/genética , Adulto JovemRESUMO
Two different rice cultivars, Yangdao 6 [Indica rice cultivar with high nitrogen-use efficiency (NUE)] and Nongken 57 (Japonica rice cultivar with low NUE) were used to study the relationship between NUE and nitrification activity in the rice seedling rhizosphere soil using a rhizobox with three compartments, and a soil-slicing method. The roots of both rice cultivars developed aerenchyma tissue [expressed as percentage porosity of root (POR)], but Yangdao 6 showed better development than Nongken 57. This root morphology change results in more radial oxygen loss (ROL) into the rhizosphere. Leaf glutamine synthetase activity (GSA) and nitrate (NO3-) reductase activity (NRA) of Yangdao 6 were significantly higher than those of Nongken 57, while there was no significant difference in root NRA between the cultivars. The nitrification activities were maximal in rhizosphere soil, followed by those in the bulk soil and the root surface for both cultivars. The rhizosphere nitrification activity, NO3- concentration and abundance of ammonia-oxidizing bacteria (AOB) associated with Yangdao 6 were always higher than those of Nongken 57. Therefore, we conclude that the greater N uptake by Yangdao 6 when compared to Nongken 57 can be mainly attributed to the bigger capacity for nitrification in Yangdao 6.
