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【medical-news】科学家发现TAp63能够抑制癌症转移
Long overshadowed by p53, its famous tumor-suppressing sibling, the p63 gene does the tougher, important job of stifling the spread of cancer to other organs, researchers at The University of Texas MD Anderson Cancer Center report in the Oct. 21 issue of Nature.
Not only does a specific form of p63 protein block metastasis, but it does so by activating the enzyme Dicer, which plays a pivotal role in the creation of micro RNAs, tiny bits of RNA that regulate a host of cellular processes.
"p63 is a master regulator of metastasis, an important role in its own right, but before now, no one understood how Dicer was regulated," said senior author Elsa R. Flores, Ph.D., associate professor in MD Anderson's Department of Cellular and Molecular Oncology.
Dicer's central role in miRNA regulation indicates the p63-Dicer connection likely has far-reaching downstream implications for many other cellular processes, Flores said. Dicer, as its name implies, slices up single pieces of non-coding RNA that then may suppress or alter coding RNA that tells the cell's protein production machinery what protein to make.
The team also demonstrated that p63 activates one miRNA that also suppresses tumor formation and metastasis. Metastatic disease accounts for about 85 percent of all deaths from cancer.
Previous studies have shown that mutant p53, commonly found in metastatic human cancer, inactivates p63. "Our findings indicate that reactivation of TAp63 in tumors lacking TAp63 expression or in those expressing mutant p53 could potentially benefit patients with metastatic disease," Flores said.
When TAp63 is missing, metastasis follows
A puzzling fact about p63 is that it's overexpressed in some tumors and underexpressed in others. Flores explained the difference depends on which form of the protein is produced. The TAp63 protein includes an area that is essential for activation of downstream target genes that protect cells from DNA damage. A second version that lacks this TA domain acts against p53, p63 and p73 genes and is associated with cancer progression.
The researchers examined the role of TAp63 by developing strains of mice lacking both copies of the TAp63 gene and others that had one intact and one knocked out version. They found:
-- Mice lacking one or both copies of TAp63 spontaneously developed carcinomas (tumors that begin on the epithelium, or lining, of an organ, the most common type of solid tumor) and sarcomas, tumors of the bone, fat, cartilage. These tumors frequently metastasized to the liver, lungs and brain, as is frequently seen in human cancer.
-- Mice lacking one or both copies of p53 develop non-metastatic tumors. Mice that have lost one copy each of p53 and TAp63 developed invasive and metastatic cancers.
-- Mice with no copies of the p53 gene that lack one or both copies of TAp63 developed highly metastatic carcinomas and sarcomas. 本人认领，48h内完成任务 Scientists Show TAp63 Suppresses Cancer Metastasis
Long overshadowed by p53, its famous tumor-suppressing sibling, the p63 gene does the tougher, important job of stifling the spread of cancer to other organs, researchers at The University of Texas MD Anderson Cancer Center report in the Oct. 21 issue of Nature.
在p53的光辉笼罩下，其同胞兄弟抑癌基因p63却在干着艰苦而重要的活——抑制肿瘤扩散到其它器官。《Nature》在10.21这期报道了来自德州大学安德森肿瘤中心的研究成果。
Not only does a specific form of p63 protein block metastasis, but it does so by activating the enzyme Dicer, which plays a pivotal role in the creation of micro RNAs, tiny bits of RNA that regulate a host of cellular processes.
p63不仅以一种特别的形式来阻断转移，而且还可以活化Dicer，后者是生产microRNA的关键酶，我们知道，很小量的microRNA在调控着胞内大量的生化过程。
"p63 is a master regulator of metastasis, an important role in its own right, but before now, no one understood how Dicer was regulated," said senior author Elsa R. Flores, Ph.D., associate professor in MD Anderson's Department of Cellular and Molecular Oncology.
“p63是（肿瘤）转移的主要抑制者，这也是其最重要的本职工作，但在此之前，没人知道Dicer是怎么被调控的”，Elsa R. Flores说道。（本文责任作者，哲学博士、MD安德森细胞分子肿瘤学部的副教授）
Dicer's central role in miRNA regulation indicates the p63-Dicer connection likely has far-reaching downstream implications for many other cellular processes, Flores said. Dicer, as its name implies, slices up single pieces of non-coding RNA that then may suppress or alter coding RNA that tells the cell's protein production machinery what protein to make.
Dicer酶在miRNA调控中的中心角色，提示p63-Dicer轴还有更广泛的下游作用，如许多其它的胞内过程， Flores解释道。 如同其名字一样，Dicer酶剪出来许多单个的非编码RNA小片段，后者可能抑制或改变编码RNA（的功能），编码RNA能告诉蛋白生产装置生产何种蛋白。
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作者:admin@医学,生命科学 2011-02-09 00:56
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