Down-regulation of 1 D-myo-inositol 1 , 4 , 5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma
Down-regulation of 1 D-myo-inositol 1 , 4 , 5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma
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口腔鳞状细胞癌中1D-肌醇1,4,5-三磷酸3-激酶A蛋白表达的下调
DOI：
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
H. Tanzawa
中科院分区：
文献类型：
--
作者：
H. Kato;K. Uzawa;Takeshi Onda;Y. Kato;Kengo Saito;D. Nakashima;K. Ogawara;H. Bukawa;H. Yokoe;H. Tanzawa
功能蛋白质组学是探索包括癌症在内的人类疾病中蛋白质表达变化的有用方法。为了确定肿瘤相关蛋白作为口腔鳞状细胞癌(OSCCs)的生物标志物或分子靶点，我们进行了双向聚丙烯酰胺凝胶电泳法和基质辅助激光解吸电离飞行时间质谱仪。比较口腔鳞癌细胞系和正常口腔角质形成细胞的蛋白质表达谱，发现了6种表达水平明显不同的蛋白质。在这六种蛋白中，我们发现了一种在口腔鳞癌细胞系中下调表达的1D-肌醇1，4，5-三磷酸3-激酶A(ITPKA)蛋白。ITPKA磷酸化1，4，5-三磷酸肌醇，它通过释放细胞内的钙离子来调节细胞内的钙离子水平，并负责调节大量在细胞信号转导中起重要作用的肌醇多磷酸的水平。免疫印迹显示ITPKA在所有被检测的口腔鳞状细胞癌细胞系中表达显著下调。实时定量逆转录聚合酶链式反应显示，在12个口腔鳞癌细胞系中有9个(75%)的ITPKA基因表达下调。免疫组织化学分析显示，100例口腔鳞癌临床标本中有40例ITPKA表达明显降低。与分化良好和分化中等的肿瘤相比，低分化肿瘤中该蛋白的免疫反应性显著降低。这些结果提示，ITPKA可能通过调节肌醇多磷酸和钙稳态与肿瘤的发生有关，ITPKA可能是临床医学中一种潜在的新的分子靶点、生物标志物、参数，或者所有这些都是细胞分化和细胞内钙稳态特性的指标。
Functional proteomics is a useful method to explore changes in protein expression in human diseases, including carcinomas. To identify tumor-associated proteins as biomarkers or molecular targets of human oral squamous cell carcinomas (OSCCs), we performed two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Comparison of the protein expression profiles of OSCC cell lines and normal oral keratinocytes identified six proteins with markedly different expression levels. Of the six proteins, we found a 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) protein that was down-regulated in OSCC cell lines. ITPKA phosphorylates inositol 1,4,5-trisphosphate, which regulates the calcium (Ca2+) level within the cell by releasing Ca2+ from intracellular stores, and is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Western blots revealed dramatically down-regulated ITPKA expression in all OSCC cell lines examined. Real-time quantitative reverse transcriptase-polymerase chain reaction showed down-regulated ITPKA mRNA expression in nine of 12 (75%) OSCC cell lines. Immunohistochemistry analysis showed that 40 of 100 OSCC clinical samples had a significant decrease in ITPKA. Poorly differentiated tumors showed significantly lower immunoreactivity of the protein compared to welland moderately-differentiated tumors. These data suggest that ITPKA may be related to carcinogenesis by the modulation of inositol polyphosphates and Ca2+ homeostasis and that ITPKA may be a potential novel molecular target, biomarker, parameter, or all of these of cellular differentiation and of intracellular Ca2+ homeostatic characteristics in clinical medicine.
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影响因子：
8
作者：
W. Wick;I. Petersen;R. Schmutzler;B. Wolfarth;D. Lenartz;E. Bierhoff;Jörg Hümmerich;Daniel J. Müller;A. Stangl;J. Schramm;Otmar D. Wiestler;A. Deimling
通讯作者：
W. Wick;I. Petersen;R. Schmutzler;B. Wolfarth;D. Lenartz;E. Bierhoff;Jörg Hümmerich;Daniel J. Müller;A. Stangl;J. Schramm;Otmar D. Wiestler;A. Deimling
从大鼠脑中纯化 D-肌醇 1,4,5-三磷酸 3-激酶。
DOI：
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发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Johanson,RA;Hansen,CA;Williamson,JR
通讯作者：
Williamson,JR
人过氧化物酶体 3-氧代酰基辅酶 A 硫解酶缺乏症。
DOI：
10.1073/pnas.84.8.2494
发表时间：
1987
影响因子：
11.1
作者：
Schram,AW;Goldfischer,S;vanRoermund,CW;Brouwer-Kelder,EM;Collins,J;Hashimoto,T;Heymans,HS;vandenBosch,H;Schutgens,RB;Tager,JM
通讯作者：
Tager,JM
体外正常和恶性人鳞状细胞抗原表达的钙调节。
DOI：
10.1001/archotol.1990.01870030063010
发表时间：
1990
期刊：
Archives of otolaryngology--head & neck surgery
影响因子：
--
作者：
Hoffman,HT;Subnani,M;Cha,M;Kidd,L;Landman,J;Tooley,R;Carey,TE
通讯作者：
Carey,TE
影响因子：
4
作者：
Tu, CL;Oda, Y;Bikle, DD
通讯作者：
Bikle, DD