3月17日,，美國科學家說，通過阻斷一種名為Skp2的基因,，能夠使癌細胞老化并死亡,。這一發(fā)現(xiàn)或許能為治療癌癥提供一種新方法。
美國哈佛大學醫(yī)學院基因學家皮耶爾·保羅·潘多爾菲介紹,，阻斷癌細胞中的Skp2基因能夠觸發(fā)“衰老進程”,，迫使癌細胞像體細胞暴露在陽光下那樣“干死”，無法無限分裂,、在人體內轉移,。
“我們發(fā)現(xiàn)，如果你(以阻斷基因方式)破壞細胞,，細胞就會生成一種內在機制,，使它們生病，”潘多爾菲說,，“這種機制以不可逆轉方式阻止它們生長,。”
潘多爾菲等研究人員以兩組老鼠為對象進行實驗。這些老鼠在基因經過改造后會患上一種前列腺癌,，但其中一組老鼠的Skp2基因遭阻斷,。6個月后，這組老鼠沒有長出腫瘤,，而Skp2基因未遭阻斷的另一組老鼠長出腫瘤,。
他們從那組沒有長腫瘤的老鼠身上提取淋巴腺和前列腺組織，發(fā)現(xiàn)其中許多癌細胞開始老化,，細胞分裂速度變慢,。
研究人員向實驗鼠體內植入人類癌細胞，結果也發(fā)現(xiàn)這些癌細胞發(fā)生老化,。
潘多爾菲說,，這種相關Skp2基因的老化進程看起來僅對癌細胞起作用，對其他細胞沒有影響,，“我們可沒打算讓癌癥患者衰老”,。
這一發(fā)現(xiàn)成果發(fā)表于最新一期《自然》Nature期刊上,。(生物谷Bioon.com)
Science：首次發(fā)現(xiàn)細胞凋亡開關 有助癌癥治療
PLoS One：美國癌癥死亡率顯著下降
Cell：肥胖者易得癌癥
生物谷推薦原文出處：
Nature doi:10.1038/nature08815
Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
Hui-Kuan Lin1,2,3, Zhenbang Chen1,2,4,6, Guocan Wang1,2,4,7, Caterina Nardella1,2,4,7, Szu-Wei Lee3,7, Chan-Hsin Chan3, Wei-Lei Yang3, Jing Wang3, Ainara Egia4, Keiichi I. Nakayama5, Carlos Cordon-Cardo2,6, Julie Teruya-Feldstein2 & Pier Paolo Pandolfi1,2,4
Cancer Biology and Genetics Program,
Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
Present addresses: Department of Biochemistry and Cancer Biology, Meharry Medical College, 1005 Dr D. B. Todd Jr Boulevard, Nashville, Tennessee 37208-3599, USA (Z.C.); Irving Cancer Research Center, Room 309, 1130 St. Nicholas Avenue, New York, New York 10032, USA (C.C.-C.).
Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19Arf–p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19Arf–p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19Arf–p53 response is impaired, whereas a Skp2–SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.
