美國研究人員發(fā)現(xiàn)了一種與乳腺癌有密切關系的基因,，這種基因是造成70%的頑固性乳腺癌的“罪魁禍首”。新發(fā)現(xiàn)將幫助科研人員研發(fā)出更有效的藥物治療乳腺癌,。
美國馬薩諸塞州懷特黑德生物醫(yī)學研究所的研究人員在本周的《自然》雜志上撰文說,，他們利用一種新技術對基因進行測試，結果發(fā)現(xiàn)了這個名為“PHGDH”的基因,。這種新技術是將具有破壞性的基因片段注入癌細胞中,，以探明哪種基因與腫瘤的形成和生長有關。
他們發(fā)現(xiàn),，在對激素療法具有抵抗力的頑固性乳腺癌細胞中,，“PHGDH”基因的活躍程度超乎尋常，結果導致癌細胞的化學成分不停地發(fā)生變化,，使激素療法失去效果,。
雌性激素可促進乳腺腫瘤生長，因此治療乳腺癌也可以用抗雌激素等藥物,，這被稱為激素療法,。但約有三分之一的乳腺癌病例是無法用激素類藥物治療的，又被稱為頑固性乳腺癌,。
研究人員指出,，一旦確定“PHGDH”基因是導致頑固性乳腺癌的“元兇”，便可研發(fā)出專門破壞這種基因活動的藥物,。(生物谷 Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature10350
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Richard Possemato; Kevin M. Marks; Yoav D. Shaul; Michael E. Pacold; Dohoon Kim; Kvan Birsoy; Shalini Sethumadhavan; Hin-Koon Woo; Hyun G. Jang; Abhishek K. Jha; Walter W. Chen; Francesca G. Barrett; Nicolas Stransky; Zhi-Yang Tsun; Glenn S. Cowley; Jordi Barretina; Nada Y. Kalaany; Peggy P. Hsu; Kathleen Ottina; Albert M. Chan; Bingbing Yuan; Levi A. Garraway; David E. Root; Mari Mino-Kenudson; Elena F. Brachtel; Edward M. Driggers; David M. Sabatini
Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation1, 2. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes3. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.
