Elucidation of a potential role of poly-ADP-ribosylation in the carcinogenesis or development of human colorectal carcinoma and its application for the diagnosis or trteatment of human colorectal carcinoma
Elucidation of a potential role of poly-ADP-ribosylation in the carcinogenesis or development of human colorectal carcinoma and its application for the diagnosis or trteatment of human colorectal carcinoma
批准号:
18591456
负责人:
NABEYA Yoshihiro
金额:
$2.04万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2006
资助国家:
日本
项目状态:
已结题
起止时间:
2006 至 2007
中文摘要
目的:聚腺苷5 '-二磷酸(ADP)-核糖基化由聚(ADP-核糖)聚合酶(PARP)催化,将聚ADP-核糖部分从烟酰胺腺嘌呤二核苷酸(NAD)转移到受体蛋白。它是一种重要的核蛋白翻译后修饰,参与包括恶性转化在内的多种生物学过程。因此,本研究的目的是评估聚ADP-核糖基化和比较PARP在人结直肠癌(CRCs)和邻近的非肿瘤mucosae.Methods的表达:肿瘤和邻近的非肿瘤组织,从手术切除的结直肠癌患者15例,然后被匀浆成细胞溶质和膜组分。用[腺苷酸-β P] -NAD测定每个匀浆的ADP-核糖基化<32>。通过电泳和放射自显影分离放射性标记的蛋白质。用阴离子交换柱层析法对ADP核糖基化蛋白进行部分纯化,并通过飞行时间质谱(TOF-MS)和免疫沉淀法进行分析。结果:在结直肠癌组织中,有几种蛋白被ADP核糖基化。值得注意的是,在CRC的胞质组分中发现了113-kDa蛋白质的显著放射性标记,并且在13/15例受试者(87%)中大于邻近非肿瘤粘膜中的放射性标记。抑制试验表明,该反应是酶促聚ADP核糖基化。通过飞行时间质谱和免疫沉淀,113 kDa的蛋白被发现是肿瘤排斥抗原,糖蛋白(gp)96。结直肠癌组织中PARP的表达明显高于癌旁组织,而gp 96的表达与癌旁组织无明显差异。结论:结直肠癌组织中gp 96的多聚ADP核糖基化和PARP的表达高于癌旁组织,可能与结直肠癌的发生发展有关。
英文摘要
Objective: Poly-adenosine 5'-diphosphate (ADP)-ribosylation, catalyzed by poly (ADP-ribose) polymerase (PARP), transfers poly-ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD) to an acceptor protein. It is an important post-translational modification of nuclear proteins and is involved in various biological processes including malignant transformation. Thus, the aim of this study was to evaluate poly-ADP-ribosylation and to compare the expression of PARP in human colorectal carcinomas (CRCs) and adjacent non-tumorous mucosae.Methods: Tumorous and adjacent non-tumorous tissues were obtained from surgically removed colorectums of 15 patients with CRC, and then were homogenized into cytosolic and membranous fractions. Each homogenate was assayed for ADP-ribosylation with [adenylate-^<32> P] -NAD. The radiolabeled proteins were separated by electrophoresis and autoradiography. The ADP-ribosylated protein was partially purified by anion exchange column chromatography, and analyzed by time-of-flight mass spectrometry (TOF-MS) and immunoprecipitation. Expression of PARP was also evaluated by Western blotting.Results: Several proteins were ADP-ribosylated in human CRC tissues. Notably, the remarkable radiolabeling of a 113-kDa protein was found in the cytosolic fractions from CRCs, and greater than that in adjacent non-tumorous mucosae in 13/15 subjects (87 %). Inhibition assays revealed that the reaction was enzymatic poly-ADP-ribosylation. By TOF-MS and immunoprecipitation, the 113-kDa protein was found to be tumor rejection antigen, glycoprotein (gp) 96. The expression of PARP was significantly greater in CRCs than in adjacent non-tumorous mucosae, while the expression of gp96 in CRCs and normal mucosae was identical.Conclusion: Poly-ADP-ribosylation of gp 96 and PARP expression were increased in human CRCs compared with those in adjacent non-tumorous mucosae, and it may be implicated in the carcinogenesis or development of human CRC.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
Enhanced poly-(adenosine 5'-diphosphate)-ribosylation of glycoprotein 96 in human colorectal carcinoma
人结直肠癌中糖蛋白 96 的聚(腺苷 5-二磷酸)核糖基化增强
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[Nabeya, Y., Inoue, M., Yahiro, K., Morinaga, N., Sakamoto, A., Noda, M. and Ochiai, T.]
通讯作者:
T.
Enhanced poly-(adenosine 5'-diphosphate)-ribosylation of glycoprotein 96 in human colorectal carcinoma.
人结直肠癌中糖蛋白 96 的聚(腺苷 5-二磷酸)核糖基化增强。
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[Nabeya, Y., Inoue, M., et. al. (other 5 authors)]
通讯作者:
et. al. (other 5 authors)
Identification of a protein which can receive poly-(adenosine 5'-diphosphate)-ribosylation in human colorectal carcinoma
人结直肠癌中可接受聚(腺苷5-二磷酸)-核糖基化的蛋白质的鉴定
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[Inoue, M., Nabeya, Y., Yahiro, K, Akai, T., Miyazaki, S., Sakamoto, A., Noda, M. and Ochiai, T.]
通讯作者:
T.
Enhanced poly- (adenosine 5'-diphosphate) -ribosylation of glycoprotein 96 in human colorectal carcinoma
人结直肠癌中糖蛋白 96 的聚(腺苷 5-二磷酸)-核糖基化增强
DOI:
--
发表时间:
2006
期刊:
Abstract DVD of 20th World Congress of International Society for Digestive Surgery 305
影响因子:
--
作者:
[Nabeya, Y., Inoue, M., Yahiro, K, Morinaga, N., Sakamoto, A., Noda, M. and Ochiai, T.]
通讯作者:
T.
ヒト大腸癌においてpoly-ADP-ribosylationを受ける蛋白の同定
人类结直肠癌中进行聚 ADP 核糖基化的蛋白质的鉴定
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[井上雅仁, 鍋谷圭宏, ほか6名]
通讯作者:
ほか6名
Genome analysis of esophageal cancer by next generation sequencer aiming for appropriately-individualized treatment
-
批准号:26462001
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$3.08万
-
财政年份:2014
-
负责人:NABEYA Yoshihiro
-
依托单位:
Mechanism of the regulation of thymidylate synthase levels associated with response to 5-fluorouracil in human gastric cancer cells
-
批准号:20591562
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.66万
-
财政年份:2008
-
负责人:NABEYA Yoshihiro
-
依托单位:
STUDIES OF POSTOPERATIVE ADJUVANT CHEMOTHERAPY BASED ON THE PREDICTION OF EFFICACY OF 5-FU-BASED CHEMOTHERAPY FOR GASTRIC CANCER.
-
批准号:12671199
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$1.98万
-
财政年份:2000
-
负责人:NABEYA Yoshihiro
-
依托单位: