Cancer cell：基底样乳腺癌的新组合治疗策略

多个研究项目包括2006年北卡罗莱纳大学教堂山分校进行的研究已采用DNA芯片分析技术，找出了几个乳腺癌亚型包括管状A型（luminal A）、管状B型，（luminal B）、基底样型和Her-2过度表达型。目前正在开发较简单的测试技术，以帮助医生确定这些亚型。近来，这些测试技术已帮助多项研究证实了基底样或三阴性乳腺癌可能在非裔美国人比白种人更流行更普遍。

UNC莱恩伯格科学家Charles Perou博士和安大略省多伦多病童医院Sean Egan带领的这项新的研究表明：一种叫做LFNG的糖转换酶的缺失会促进基底样乳腺癌细胞增殖和肿瘤的形成。这项研究上周发表在Cancer Cell杂志上。

在实验室动物模型研究中，去除LFNG不仅会引起肿瘤的形成，同时也激活两个对肿瘤形成的重要细胞信号通路。该研究小组发现去除LFNG后，Notch信号的激活和met原癌基因的表达同时也增加了。

Perou博士说：这是令人兴奋，因为靶向这些信号途径的药物正在开发。虽然作用于每个信号通路可能发挥作用，但我们的研究结果表明联合治疗可能是治疗基底样肿瘤很有前途的策略。

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.