RESUMEN
Background: The aim of this study was to investigate associations between polymorphisms in the Lysyl oxidase (LOX) gene with susceptibility to cancer. The role of LOX in carcinogenesis prompted several association studies in various cancer types; however the outcomes of these studies have inconsistent. Thus, we performed a meta-analysis to obtain more precise estimates. Materials and Methods: A literature search yielded 14 articles from which we examined five cancer groups: breast, bone, lung, gastrointestinal, and gynecological cancers. For each cancer group, pooled odds ratios (ORs) and confidence intervals (95% CIs) were calculated using standard genetic models. High significance (p-value for association [pa] < 0.00001), homogeneity (I2 = 0%), and high precision of effects (CI difference [CID] <1.0 [upper CI - lower CI]) comprised the three criteria for strength of evidence. We used sensitivity analysis to assess robustness of the outcomes. Results: We generated 28 comparisons from which 13 were significant (pa < 0.05), indicating increased risk, (OR >1.00) found in all cancer groups except breast (pa = 0.10-0.91). Of the 13, three met all criteria (core) for strength of evidence (pa < 0.00001, CIDs 0.49-0.56 and I2 = 0%), found in dominant/codominant models of gynecological cancers (ORs 1.52-1.62, 95% CIs 1.26-1.88) and codominant model of lung cancer (OR 1.44, 95% CI 1.19-1.74). These three were deemed robust. Conclusion: Based on the three core outcomes, associations of LOX 473G/A with lung, ovarian, and cervical cancers indicate 1.4-1.6-fold increased risks, underpinned by robustness and high statistical power at the aggregate level.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinogénesis/genética , Predisposición Genética a la Enfermedad , Neoplasias/genética , Proteína-Lisina 6-Oxidasa/genética , Humanos , Neoplasias/epidemiología , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricosRESUMEN
Membrane proteins of amino acid-polyamine-organocation (APC) superfamily transport amino acids and amines across membranes and play important roles in the regulation of cellular processes. The alanine or glycine: cation symporter (AGCS) family belongs to APC superfamily and is found in prokaryotes, but its substrate specificity remains to be clarified. In this study, we found that a halotolerant cyanobacterium, Aphanothece halophytica has two putative ApagcS genes. The deduced amino acid sequence of one of genes, ApagcS1, exhibited high homology to Pseudomonas AgcS. The ApagcS1 gene was expressed in Escherichia coli JW4166 which is deficient in glycine uptake. Kinetics studies in JW4166 revealed that ApAgcS1 is a sodium-dependent glycine transporter. Competition experiments showed the significant inhibition by glutamine, asparagine, and glycine. The level of mRNA for ApagcS1 was induced by NaCl and nitrogen-deficient stresses. Uptake of glutamine by ApAgcS1 was also observed. Based on these data, the physiological role of ApAgcS1 was discussed.
Asunto(s)
Alanina/metabolismo , Proteínas Bacterianas/metabolismo , Cianobacterias/fisiología , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Glicina/metabolismo , Proteínas Bacterianas/genética , Transporte Biológico , Clonación Molecular , Cianobacterias/genética , Cianobacterias/metabolismo , Escherichia coli/citología , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Proteínas de Transporte de Glicina en la Membrana Plasmática/genética , Cinética , Nitrógeno/deficiencia , Salinidad , Sodio/metabolismo , Estrés Fisiológico , Especificidad por Sustrato , Regulación hacia ArribaRESUMEN
Alkaliphilic halotolerant cyanobacterium Aphanothece halophytica showed optimal growth in the medium containing 0.5 M NaCl. The increase of exogenously added glycine to the medium up to 10 mM significantly promoted cell growth under both normal (0.5 M NaCl) and salt stress (2.0 M NaCl) conditions. Salt stress imposed by either 2.0 or 3.0 M NaCl retarded cell growth; however, exogenously added glycine at 10 mM concentration to salt-stress medium resulted in the reduction of growth inhibition particularly under 3.0 M NaCl condition. The uptake of glycine by intact A. halophytica was shown to exhibit saturation kinetics with an apparent K s of 160 µM and V max of 3.9 nmol/min/mg protein. The optimal pH for glycine uptake was at pH 8.0. The uptake activity was decreased in the presence of high concentration of NaCl. Both metabolic inhibitors and ionophores decreased glycine uptake in A. halophytica suggesting an energy-dependent glycine uptake. Several neutral amino acids showed considerable inhibition of glycine uptake with higher than 50 % inhibition observed with serine, cysteine and alanine whereas acidic, basic and aromatic amino acids showed only slight inhibition of glycine uptake.
