在日前在線出版的《自然·細(xì)胞生物學(xué)》期刊上,，科學(xué)家們報(bào)告說,，他們鑒別出導(dǎo)致一種特殊進(jìn)展性乳腺癌形成的因子。在炎性乳腺癌患者體內(nèi),，一種蛋白質(zhì)調(diào)控子的過多出現(xiàn)誘導(dǎo)了某種細(xì)胞黏滯因子出現(xiàn),。這些因子會(huì)將細(xì)胞轉(zhuǎn)變?yōu)檗D(zhuǎn)移瘤。新發(fā)現(xiàn)有助于研制新的靶向療法,，阻止這種類型的癌癥的擴(kuò)散,。
由于擴(kuò)散速度快速，炎性乳腺癌是一種最為致命的乳腺癌癥,。Robert Schneider和同事的研究顯示,，炎性乳腺癌的特征之一是一種名為eIF4GI的蛋白質(zhì)的過度表達(dá)。他們發(fā)現(xiàn),，盡管這種因子不會(huì)影響全部蛋白質(zhì)的產(chǎn)出,，但它會(huì)導(dǎo)致細(xì)胞黏滯調(diào)控子E-cadherin和連環(huán)蛋白p120ctn的增加，它們讓癌細(xì)胞聚成團(tuán)簇而不是附著在附近的細(xì)胞上,。這些癌細(xì)胞團(tuán)簇進(jìn)入循環(huán)系統(tǒng),，并通過一種被動(dòng)轉(zhuǎn)移過程擴(kuò)散到身體各組織，最終導(dǎo)致炎性乳腺癌的發(fā)生,。對(duì)癌癥模型小鼠的實(shí)驗(yàn)顯示,，遏制eIF4GI,、E-cadherin或p120ctn的活性，均能破壞腫瘤的生長(zhǎng)和入侵,。作者指出,，eIF4GI在乳腺癌中的作用依賴于p120ctn調(diào)控的松懈。
以炎性乳腺癌的導(dǎo)致分子為靶標(biāo),，有助于開發(fā)治療型干擾術(shù),，阻止這種特殊進(jìn)展性乳腺癌的擴(kuò)散。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology 11, 903 - 908 (2009) 14 June 2009 | doi:10.1038/ncb1900
Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer
Deborah Silvera1, Rezina Arju1, Farbod Darvishian2, Paul H. Levine3, Ladan Zolfaghari3, Judith Goldberg4, Tsivia Hochman4, Silvia C. Formenti5,6 & Robert J. Schneider1,6
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer1. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis2, 3, 4, 5. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential6, 7. In IBC, E-cadherin is overexpressed8 and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma2, 3, 9. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer.
1 Department of Microbiology New York University School of Medicine, New York, New York, 10016, USA.
2 Department of Pathology, New York University School of Medicine, New York, New York, 10016, USA.
3 George Washington University School of Public Health, Washington, District of Columbia, 20037, USA.
4 Department of Environmental Medicine, Division of Biostatistics, New York, New York, 10016, USA.
5 Department of Radiation Oncology New York, New York, 10016, USA.
6 NYU Cancer Institute, New York University School of Medicine, New York, New York, 10016, USA.
