最近,英国和加拿大的研究人员合作研究发现,一种名为ZNF703的基因过度活跃,会导致乳腺癌。研究人员称,这是科学家5年来发现的首个乳腺癌致癌基因,对于乳腺癌的治疗极具意义。相关研究成果发表在2月18日《欧洲分子生物学学会期刊》上。
由英国剑桥大学和加拿大不列颠哥伦比亚大学的研究人员组成的研究小组,使用微阵列芯片技术,同时对大量的细胞组织样本测试,通过乳腺癌肿瘤细胞与正常健康细胞中基因活性的对比,他们发现,一种名为ZNF703的基因在雌激素受体阳性乳腺癌肿瘤中极其活跃。通过分析,研究人员判定,ZNF703是一个新的雌激素受体阳性乳腺癌驱动基因。
研究人员认为,测试ZNF703基因活性,有助于判断癌症病人肿瘤发展情况,据此可设计针对性治疗方案。而这一发现如经更大规模的研究获得证实,将为开发出新的以ZNF703基因为标靶的癌症治疗手段铺平道路。
研究论文首席作者、英国剑桥大学的卡洛斯·卡尔达斯教授指出,通过测试这种基因的活跃程度,可使医生了解标准激素疗法,如使用它莫西芬(一种抗雌激素)或者芳香酶抑制剂是否有效,从而帮助医生确认符合病人病情的针对性药物。
英国癌症研究所的莱斯利·沃尔克博士则表示,ZNF703是5年来发现的首个乳腺癌致癌基因,对于开发新的乳腺癌治疗药物十分重要,希望能藉此开发出更有效的癌症治疗手段。(生物谷Bioon.com)
生物谷推荐原文出处:
EMBO Molecular Medicine DOI: 10.1002/emmm.201100122
ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium
Daniel G. Holland1,2, Angela Burleigh3,4, Anna Git1,2, Mae A. Goldgraben1,2, Pedro A. Perez-Mancera1,2, Suet-Feung Chin1, Antonio Hurtado1, Alejandra Bruna1,2, H. Raza Ali1,2, Wendy Greenwood1,2, Mark J. Dunning1, Shamith Samarajiwa1, Suraj Menon1, Oscar M. Rueda1,2, Andy G. Lynch1, Steven McKinney3,4, Ian O. Ellis5, Connie J. Eaves3,4, Jason S. Carroll1,2, Christina Curtis1,8, Samuel Aparicio3,4, Carlos Caldas1,2,6,7
Keywords:breast cancer;oestrogen metabolism;Luminal B;oncogene;ZNF703
The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGFβ on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.