上海 2012年8月10日 訊 /生物谷BIOON/ 通過(guò)新的涉及小線蟲(chóng)的實(shí)驗(yàn)，懷俄明州的科學(xué)家們已經(jīng)發(fā)現(xiàn)了幾個(gè)基因可能是開(kāi)發(fā)抗癌癥藥物的潛在靶標(biāo),。具體來(lái)說(shuō),，研究人員推測(cè)抑制這些基因可能扭轉(zhuǎn)癌細(xì)胞的某些關(guān)鍵特征。
拉勒米懷俄明大學(xué)分子生物學(xué)系研究員David S. Fay博士說(shuō)：癌癥是全球主要的死亡原因,，我們希望通過(guò)開(kāi)展基本的遺傳研究來(lái)發(fā)現(xiàn)與癌癥牽密切相關(guān)聯(lián)的最全面的基因,，以此來(lái)開(kāi)發(fā)治療多種癌癥的各種治療方法。
Fay博士和他同事利用體內(nèi)存在類(lèi)似許多人癌癥中滅活的基因的線蟲(chóng)進(jìn)行研究,。這各基因在蠕蟲(chóng)中稱(chēng)為L(zhǎng)IN-35,，在人身上稱(chēng)為PRB，該基因被認(rèn)為能控制腫瘤進(jìn)展的各個(gè)方面包括癌癥細(xì)胞的生長(zhǎng)和生存,。研究人員系統(tǒng)地滅活LIN-35基因突變的蠕蟲(chóng)其它單個(gè)基因,，當(dāng)他們抑制各種基因時(shí)，科學(xué)家發(fā)現(xiàn)那些由于LIN-35缺失導(dǎo)致的缺陷能被逆轉(zhuǎn),，這表明LIN-35可以作為抗癌療法的靶標(biāo),。
GENETICS期刊首席編輯Mark Johnston說(shuō)：這項(xiàng)研究很有意義，因?yàn)樗沂玖艘环N能關(guān)閉有助于腫瘤生長(zhǎng)和發(fā)展的遺傳機(jī)制的方法,。癌癥的發(fā)病原因是復(fù)雜多樣的,，所以我們必須從多角度來(lái)研究這種疾病。使用簡(jiǎn)單的模式生物如線蟲(chóng)以尋找新的藥物靶標(biāo)正變得日益重要,。（生物谷：Bioon.com）
編譯自：Scientists Use Worms to Unearth Cancer Drug Targets
doi:10.1534/genetics.112.140152
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PMID:
A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans.
S. R. G. Polley, D. S. Fay
The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities
