大鼠肝癌变进程中差异表达序列标签的初步筛选及分析
摘要
目的:采用mRNA差异显示反转录聚合酶链式反应技术(DDRT-PCR)筛选大鼠肝癌变不同时期的差异表达序列标签(Express sequence tags, ESTs),探索肝癌发生和发展的分子机理。
方法:用二乙基亚硝胺(Diethylnitrosamine, DENA)作诱癌剂建立SD大鼠肝癌变不同时期的动物模型。自给药起,分别在14d、28d、56d、77d、105d、112d处死大鼠,取其肝组织,用mRNA差异显示技术(DDRT-PCR)研究不同病理时期差异表达的基因,克隆与测序后用生物信息学方法对测序结果进行分析。
结果:获得12条差异表达片段。其中有3个片段(EST-1,EST-3,EST-5)在大鼠ESTs数据库和基因组数据库中均未找到同源序列,可能是新基因片段;有1个差异表达片段EST-12在大鼠ESTs数据库中未找到同源序列,但与基因组数据库中的蛋白激酶C- alpha基因有95%的同源性,可以认为是该基因的同源序列,可作为大鼠新的EST;有2个差异表达片段EST-7和EST-11分别与大鼠BN/SsNHsdMCW线粒体基因片段和酪氨酸/色氨酸单加氧酶激酶基因片段同源性达100%,可以认为分别是上述二种基因的部分序列,但BN/SsNHsdMCW线粒体基因编码蛋白尚未知晓;其余6个差异表达片段(EST-2、EST、EST-6、EST-8、EST-9和EST-10)在大鼠已知ESTs数据库和基因组数据库中的均找到与其同源达97%以上的序列,可以认为是已知基因的同源序列。
结论:初步筛选出12个肝癌变进程中差异表达的ESTs,其中9个为已知基因片段, 3个为新基因片段。EST-7与大鼠线粒体BN/SsNHsdMCW基因片段同源性达100%,可以认为是该基因的一段序列。本研究首次发现线粒体BN/SsNHsdMCW基因在大鼠肝癌变各时期的差异表达情况。
PURPOSE: To reveal the molecular mechanism of carcinogenesis, we screened and analyzed differentially expressed sequence tags (ESTs) in rats’primary hepatic cancer induced by a differential display of messenger RNA (DDRT-PCR) technique.
METHODS: Using diethylnitrosamine (DENA) as an induced regent, the animal models of the various periods during the development of SD rats’primary hepatic cancer were made. The rats’were and killed on 14th day, 28th day, 56th day, 77th day, 105th day and 112th day respectively from the first day when the rats were piped drinking and the liver tissue of every rat was taken after killed. DDRT-PCR was used to research the differential expression of the genes between the normal tissue and the morbid tissue. After screened, the differential expressed fragments obtained from the experiments were cloned and sequenced. The results were analyzed by bioinformatics.
RESULTS: 12 cDNA fragments were obtained from the experiments. EST-1, EST-3 and EST-5 had extremely low sequence identity with any genes from GenBank database. EST-12 had no similar sequence from rattus norvegicus ESTs database, while it was similar to partial sequence of PKC-alpha gene in the rat build 4 genome database. EST-7 was similar to rattus norvegicus strain BN/SsNHsdMCW mitochondrion gene (100%), its homologous proteins is unknown. EST-11 was similar to tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide, and the identity was also 100%. The res(tEST-2、EST、EST-6、EST-8、EST-9 and EST-10) had similar sequences in both databases, and all the identities exceeded 97%.
CONCLUSIONS: Twelve ESTs differentially expressed during the different periods of liver canceration were obtained, nine of these are known, others are unknown. EST-7 was similar to BN/SsNHsdMCW mitochondrion gene and the identity was 100%. It was the first report of differentially expressed mRNA of BN/SsNHsdMCW mitochondrion gene in all the liver canceration periods, and the complex variation of this gene suggests it may take part in the carcinogenesis and development of primary hepatic cancer and possibly play a part in the mechanism of the cellular multiplication and malignant transformation.
方法:用二乙基亚硝胺(Diethylnitrosamine, DENA)作诱癌剂建立SD大鼠肝癌变不同时期的动物模型。自给药起,分别在14d、28d、56d、77d、105d、112d处死大鼠,取其肝组织,用mRNA差异显示技术(DDRT-PCR)研究不同病理时期差异表达的基因,克隆与测序后用生物信息学方法对测序结果进行分析。
结果:获得12条差异表达片段。其中有3个片段(EST-1,EST-3,EST-5)在大鼠ESTs数据库和基因组数据库中均未找到同源序列,可能是新基因片段;有1个差异表达片段EST-12在大鼠ESTs数据库中未找到同源序列,但与基因组数据库中的蛋白激酶C- alpha基因有95%的同源性,可以认为是该基因的同源序列,可作为大鼠新的EST;有2个差异表达片段EST-7和EST-11分别与大鼠BN/SsNHsdMCW线粒体基因片段和酪氨酸/色氨酸单加氧酶激酶基因片段同源性达100%,可以认为分别是上述二种基因的部分序列,但BN/SsNHsdMCW线粒体基因编码蛋白尚未知晓;其余6个差异表达片段(EST-2、EST、EST-6、EST-8、EST-9和EST-10)在大鼠已知ESTs数据库和基因组数据库中的均找到与其同源达97%以上的序列,可以认为是已知基因的同源序列。
结论:初步筛选出12个肝癌变进程中差异表达的ESTs,其中9个为已知基因片段, 3个为新基因片段。EST-7与大鼠线粒体BN/SsNHsdMCW基因片段同源性达100%,可以认为是该基因的一段序列。本研究首次发现线粒体BN/SsNHsdMCW基因在大鼠肝癌变各时期的差异表达情况。
PURPOSE: To reveal the molecular mechanism of carcinogenesis, we screened and analyzed differentially expressed sequence tags (ESTs) in rats’primary hepatic cancer induced by a differential display of messenger RNA (DDRT-PCR) technique.
METHODS: Using diethylnitrosamine (DENA) as an induced regent, the animal models of the various periods during the development of SD rats’primary hepatic cancer were made. The rats’were and killed on 14th day, 28th day, 56th day, 77th day, 105th day and 112th day respectively from the first day when the rats were piped drinking and the liver tissue of every rat was taken after killed. DDRT-PCR was used to research the differential expression of the genes between the normal tissue and the morbid tissue. After screened, the differential expressed fragments obtained from the experiments were cloned and sequenced. The results were analyzed by bioinformatics.
RESULTS: 12 cDNA fragments were obtained from the experiments. EST-1, EST-3 and EST-5 had extremely low sequence identity with any genes from GenBank database. EST-12 had no similar sequence from rattus norvegicus ESTs database, while it was similar to partial sequence of PKC-alpha gene in the rat build 4 genome database. EST-7 was similar to rattus norvegicus strain BN/SsNHsdMCW mitochondrion gene (100%), its homologous proteins is unknown. EST-11 was similar to tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide, and the identity was also 100%. The res(tEST-2、EST、EST-6、EST-8、EST-9 and EST-10) had similar sequences in both databases, and all the identities exceeded 97%.
CONCLUSIONS: Twelve ESTs differentially expressed during the different periods of liver canceration were obtained, nine of these are known, others are unknown. EST-7 was similar to BN/SsNHsdMCW mitochondrion gene and the identity was 100%. It was the first report of differentially expressed mRNA of BN/SsNHsdMCW mitochondrion gene in all the liver canceration periods, and the complex variation of this gene suggests it may take part in the carcinogenesis and development of primary hepatic cancer and possibly play a part in the mechanism of the cellular multiplication and malignant transformation.
引文
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