RESUMEN
Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.
Asunto(s)
Neoplasias de la Mama/genética , Receptor alfa de Estrógeno/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , Persona de Mediana EdadRESUMEN
Our study aimed to investigate the co-localization and protein-protein interactions between ezrin and p65 in human breast cancer cells. Liquid chromatography-mass spectrometry (LCMS) was used to uncover novel protein interactions with ezrin in MDA-MB-231 cells. Endogenous co-immunoprecipitation was used to validate protein-protein interactions between ezrin and p65 in MDA-MB-231. Exogenous interactions between ezrin and p65 were validated in MDA-MB-231 cells via Flag-ezrin and HA-p65 co-transfection and followed by co-immunoprecipitation. Immunofluorescence staining was used to visualize ezrin and p65 co-localization in MDA-MB-231. LCMS results showed that there were 1000 proteins interacting with ezrin in MDA-MB-231 cells. Ezrin and p65 interactions were confirmed with both endogenous and exogenous methods. We were also able to visualize ezrin and p65 co-localization in MDA-MB-231. In summary, we found protein-protein interactions between Ezrin and p65 in human breast cancer cells.
Asunto(s)
Neoplasias de la Mama/metabolismo , Proteínas del Citoesqueleto/metabolismo , Factor de Transcripción ReIA/metabolismo , Línea Celular Tumoral , Humanos , Unión ProteicaRESUMEN
Evidence suggests that some genetic variants are risk factors for both colorectal cancer (CRC) and gastric cancer (GC). Thus, we selected 12 reported single nucleotide polymorphisms (SNPs) from genome-wide association studies of CRC and conducted this case-control study to assess the associations between these SNPs and the risk for GC in a southern Chinese population. All SNPs were genotyped in 249 individuals with GC and 292 healthy population-matched subjects using the Sequenom MassArray iPLEX System. Association analyses based on the c2 test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. A stratified analysis by gender was also performed. Borderline significant associations were observed for rs4444235 (P = 0.070) and rs10411210 (P = 0.084), both fitting the overdominant model. The rs4444235 CT genotype showed a protective effect (OR = 0.72, 95%CI = 0.50-1.03), while the rs10411210 CT genotype was a risk factor (OR = 1.40, 95%CI = 0.96-2.05) as compared with the CC+TT genotype. In the female subgroup, the rs6983267 GT genotype (compared with TT, OR = 2.31, 95%CI = 1.07-4.99) and the rs10505477 CT genotype (compared with TT, OR = 2.36, 95%CI = 1.09-5.11) significantly increased the risk for GC. No significant association was detected for the other SNPs. These results provide evidence that known genetic variants associated with CRC risk may also confer risk for GC.
Asunto(s)
Neoplasias Colorrectales/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Neoplasias Gástricas/genética , Adulto , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Caracteres Sexuales , Neoplasias Gástricas/patologíaRESUMEN
As a model plant, mechanisms of the cytoplasmic male sterility/restoration of fertility (CMS/Rf) system in tobacco are seldom studied. Using Rf gene sequences from other Solanaceae plants and the draft genome of Nicotiana benthamiana, degenerate primers were designed to amplify the cDNA pool of N. tomentosiformis. In total, six possible Rf sequences were identified, two of which contained base-deletion mutations. The other four were intact open reading frames, of which NtomPPR5 harbored a 3-pentatricopeptide repeat (PPR) motif deletion. Structure analysis revealed that they all encoded a PPR-containing protein with putative mitochondrial targeting signals at their N-terminus, and they all belong to the P subfamily. Phylogenetic analysis showed that all of the Rf-coding PPRs clustered together, and recent duplication events might have occurred in tobacco after the divergence of the species. Quantitative reverse transcription polymerase chain reaction analysis demonstrated that the NtomRfs were expressed in all tissues of N. tomentosiformis and (CMS) K326, although the expression levels varied with gene, organ, and developmental stage. Furthermore, the expression levels of Rf sequences in K326 were lower than those in CMS K326. The molecular basis of the CMS/Rf system in tobacco requires further investigation.
Asunto(s)
Clonación Molecular , Expresión Génica , Nicotiana/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Dominios y Motivos de Interacción de Proteínas/genética , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Secuencia de Bases , Secuencia de Consenso , Datos de Secuencia Molecular , Familia de Multigenes , Filogenia , Posición Específica de Matrices de Puntuación , Nicotiana/clasificaciónRESUMEN
A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.