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Background and purpose:Lung cancer is one of the leading causes of cancer death in the world. The aim of this study was to evaluate whether Fas-670 G>A and Fasl-844 T>C polymorphisms were associated with the risk of lung cancer.Methods:Data from 400 lung cancer patients with speciifc histological diagnosis were collected from 2010 to 2015. Meanwhile, data from matched healthy controls with the same gender and ±5 years were also collected. The genotypes of Fas-670 G>A and Fasl-844 T>C polymorphisms were determined by TaqMan lfuorescent probe method, and the results were analyzed using SPSS 16.0 software.Results:A total number of 386 cases and 394 controls were successfully genotyped. Compared with AA genotypeofFasgene, the GA and GG genotype carriers had no signiifcantly increased risk of lung cancer.The OR values were 1.05 (95%CI: 0.77-1.44) and 0.77 (95%CI: 0.81-1.99) respectively. Compared with TT genotype ofFasl gene, the CT and CC genotype carriers had signiifcantly increased risk of lung cancer. The OR values were 1.37 (95%CI: 1.01-1.86) and 1.74 (95%CI: 1.09-2.77), respectively. Conclusion:Fasl-844 T>C polymorphism may be involved in lung cancer risk but not Fas-670 G>A polymorphism.
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Potential markers for progression of pulmonary squamous cell carcinoma (SCC) were identified by examining samples of lung SCC and adjacent normal tissues using a combination of fluorescence two-dimensional difference gel electrophoresis (2D-DIGE), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and electrospray ionization quadrupole-time of flight mass spectrometry (ESI-Q-TOF). The PANTHER System was used for gel image based quantification and statistical analysis. An analysis of proteomic data revealed that 323 protein spots showed significantly different levels of expression (P ≤ 0.05) in lung SCC tissue compared to expression in normal lung tissue. A further analysis of these protein spots by MALDI-TOF-MS identified 81 different proteins. A systems biology approach was used to map these proteins to major pathways involved in numerous cellular processes, including localization, transport, cellular component organization, apoptosis, and reproduction. Additionally, the expression of several proteins in lung SCC and normal tissues was examined using immunohistochemistry and western blot. The functions of individual proteins are being further investigated and validated, and the results might provide new insights into the mechanism of lung SCC progression, potentially leading to the design of novel diagnostic and therapeutic strategies.
Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Proteômica , Microambiente Tumoral/genética , Adulto , Idoso , Sequência de Aminoácidos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Eletroforese em Gel Bidimensional , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Dados de Sequência Molecular , Proteínas de Neoplasias/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
p53 is an important molecule in cellular response to DNA damage. After genotoxic stress, p53 protein stabilizes transiently and accumulates in the nucleus, where it functions as a transcription factor and upregulates multiple downstream-targeted genes, including p21(Waf1/Cip1), Gadd45a and Bax. However, regulation of p53 stabilization is complex and may mainly involve post-translational modification of p53, such as phosphorylation and acetylation. Using mouse embryonic fibroblasts (MEFs) derived from Gadd45a knockouts, we found that disruption of Gadd45a greatly abolished p53 protein stabilization following UVB treatment. Phosphorylation of p53 at Ser-15 was substantially reduced in Gadd45a-/- MEFs. In addition, p53 induction by UVB was shown to be greatly abrogated in the presence of p38 kinase inhibitor, but not c-Jun N-terminal kinase (JNK) and extracellular-signal regulated kinase (ERK), suggesting that p38 protein kinase is involved in the regulation of p53 induction. Along with the findings presented above, inducible expression of Gadd45a enhanced p53 accumulation after cell exposure to UVB. Taken together, the current study demonstrates that Gadd45a, a conventional downstream gene of p53, may play a role as an upstream effector in p53 stabilization following DNA damage, and thus has defined a positive feedback signal in the activation of the p53 pathway.
Assuntos
Proteínas de Ciclo Celular , Proteínas Nucleares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Dano ao DNA/efeitos da radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Camundongos , Raios UltravioletaRESUMO
Objective In many types of epithelial tumors,down-regulation or mutation of the epithelial cell-adherent molecule E-cadherin is associated with an increased invasiveness that can be prevented by the forced expression of the cell-adherent molecule.This suggests that E-cadherin is a latestage tumor suppressor that prevents invasion and metastasis.This study was to investigate cell invasion and migration status of human ovary serous cystadeno carcinoma HO-8910 cell line when the E-cadherin expression was down-regulated with RNA interference(RNAi) technology. Methods E-cadherin siRNA was transfected into HO-8910 cells to inhibit the expression of E-cadherin.The effect of RNAi was detected by immunofluoresence assay and Western blotting.The invasive ability of the cancer cells was determined by Transwell assay. Results After RNAi,the expressions of E-cadherin were significantly decreased from 63.7% to 11.9%(P
