ABSTRACT
Background and purpose:Rs10993994 at 10q11 was found to be associated with prostate cancer risk by genome-wide association studies. This study tried to reveal its mechanism and to explore the role of rs10993994 for the transcriptional activity of microseminoprotein beta (MSMB) gene in prostate cancer cell lines. Methods:Promoter fragments were generated by chemical synthesis. Due to the two possibility of rs10993994 (T/C) in the region, we generated two promoter fragments: MSMB promoter-T and MSMB promoter-C. The fragments were then cloned into pGL3-basic vectors, positive clones were transfected into prostate cancer cell lines PC-3 and LNCaP, ifnally, relative level of lfuorescence was detected by lfuoresce detector.Results:We generated two promoter fragments of MSMB, MSMB promoter-T and MSMB promoter-C. The two promoter fragments were cloned with pGL3-basic vectors to pGL3-MSMB promoter-T and pGL3-MSMB promoter-C. In PC-3, the relative level of lfuorescence of pGL3-MSMB promoter-C was signiifcant higher than that of pGL3-MSMB promoter-T(2.27±0.39vs 0.57±0.13,P<0.05); In LNCaP, the relative level of lfuorescence of pGL3-MSMB promoter-C was signiifcant higher than that of pGL3-MSMB promoter-T (1.70±0.32vs 0.37±0.09,P<0.05).Conclusion:The transcriptional activity of pGL3-MSMB promoter-C was stronger than that of pGL3-MSMB promoter-T. Rs10993994 could inlfuence the transcriptional activity ofMSMB gene promoter in prostate cancer cell lines PC-3 LNCaP, allele C in rs10993994 could facilitate transcription than T.
ABSTRACT
Objective To explore the correlation between ITGA6 gene (rs12621278, G), MSMB gene (rs10993994, T), chromosome 8q24 (rs10086908, T) and prostate cancer (PCa) in Beijing residents, and to explore the correlation between genotype and phenotype in PCa patients. Methods PCa patient phenotypes were collected including clinical, genetic, dietary habits, hobbies and blood samples. ITGA6 gene (rs12621278, G), chromosome 8q24 (rs10086908, T) and MSMB gene (rs10993994, T) compared the allele distribution between 112 PCa and 91 healthy control age matched patients. The genotype and phenotype analysis was conducted in the 2 groups. Results Between the case and control groups, only rs10993994, T of MSMB gene (case 56.4%,control 46.2%) was significantly different (P=0.001; OR=1.97, 95%CI:1.28-3.04). The rs10086908, T of 8q24 (case 83.5%, control 79.2%) and rs12621278, G of ITGA6 gene (case 27.2%, control 27.0%) were not significantly associated with PCa in the study sample (P>0.05). Quantitative trait analysis showed that the disease duration of ITGA6 risk genotypes (G/G,1.40±0.55 years) in PCa patients was significantly shorter (P=0.003) than the other genotype carriers (A/G, 4.38±3.10 years; A/A, 2.37±1.84 years). Conclusion The genetic variation in MSMB is possibly associated with PCa susceptibility, suggesting that MSMB genes might be associated with PCa in a Chinese population.