多個(gè)研究項(xiàng)目包括2006年北卡羅萊納大學(xué)教堂山分校進(jìn)行的研究已采用DNA芯片分析技術(shù),，找出了幾個(gè)乳腺癌亞型包括管狀A(yù)型（luminal A）、管狀B型，（luminal B）,、基底樣型和Her-2過(guò)度表達(dá)型。目前正在開發(fā)較簡(jiǎn)單的測(cè)試技術(shù),，以幫助醫(yī)生確定這些亞型,。近來(lái)，這些測(cè)試技術(shù)已幫助多項(xiàng)研究證實(shí)了基底樣或三陰性乳腺癌可能在非裔美國(guó)人比白種人更流行更普遍,。
UNC萊恩伯格科學(xué)家Charles Perou博士和安大略省多倫多病童醫(yī)院Sean Egan帶領(lǐng)的這項(xiàng)新的研究表明：一種叫做LFNG的糖轉(zhuǎn)換酶的缺失會(huì)促進(jìn)基底樣乳腺癌細(xì)胞增殖和腫瘤的形成,。這項(xiàng)研究上周發(fā)表在Cancer Cell雜志上。
在實(shí)驗(yàn)室動(dòng)物模型研究中,，去除LFNG不僅會(huì)引起腫瘤的形成,，同時(shí)也激活兩個(gè)對(duì)腫瘤形成的重要細(xì)胞信號(hào)通路。該研究小組發(fā)現(xiàn)去除LFNG后,，Notch信號(hào)的激活和met原癌基因的表達(dá)同時(shí)也增加了,。
Perou博士說(shuō)：這是令人興奮，因?yàn)榘邢蜻@些信號(hào)途徑的藥物正在開發(fā),。雖然作用于每個(gè)信號(hào)通路可能發(fā)揮作用,，但我們的研究結(jié)果表明聯(lián)合治療可能是治療基底樣腫瘤很有前途的策略。（生物谷：Bioon.com）
doi:10.1016/j.ccr.2012.03.041
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Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-like Breast Cancer
Keli Xu, Jerry Usary, Philaretos C. Kousis, Aleix Prat, Dong-Yu Wang, Jessica R. Adams, Wei Wang, Amanda J. Loch, Tao Deng, Wei Zhao, Robert Darrell Cardiff, Keejung Yoon, Nicholas Gaiano, Vicki Ling, Joseph Beyene, Eldad Zacksenhaus, Tom Gridley, Wey L. Leong, Cynthia J. Guidos, Charles M. Perou, Sean E. Egan
Basal-like breast cancers (BLBC) express a luminal progenitor gene signature. Notch receptor signaling promotes luminal cell fate specification in the mammary gland, while suppressing stem cell self-renewal. Here we show that deletion of Lfng, a sugar transferase that prevents Notch activation by Jagged ligands, enhances stem/progenitor cell proliferation. Mammary-specific deletion of Lfng induces basal-like and claudin-low tumors with accumulation of Notch intracellular domain fragments, increased expression of proliferation-associated Notch targets, amplification of the Met/Caveolin locus, and elevated Met and Igf-1R signaling. Human BL breast tumors, commonly associated with JAGGED expression, elevated MET signaling, and CAVEOLIN accumulation, express low levels of LFNG. Thus, reduced LFNG expression facilitates JAG/NOTCH luminal progenitor signaling and cooperates with MET/CAVEOLIN basal-type signaling to promote BLBC.
