来自德克萨斯大学M.D. Anderson癌症中心的研究人员发现了一个单独的基因，可以作为以前没有确定下来的肿瘤的抑制子。这个基因可以执行一个关键的作用，引发人类基因组的两种DNA损伤检测和修复途径。这一研究成果公布在Cancer Cell杂志上。
研究人员说一种被称为BRIT1的基因被发现在人类的卵巢，乳房和前列腺癌症细胞系低表达。作者表示缺失了BRIT1基因看上去是对癌症的起始和进程是一个关键的改变，更深的理解这个基因的功能可以对未来的治疗癌症的方法有一个显著的贡献。
这项研究的作者，分子治疗学的助理教授Shiaw-Yih Lin说到，“破坏了BRIT1基因的功能就可以消除DNA损伤反应以及随之带来的基因组的不稳定性。”而基因组的不稳定性的后果就是带来癌症细胞的起始，增殖和扩散。
英文原文：
Researchers identify gene as DNA guardian and sworn enemy of tumours
This latest discovery represents another potential target for cancer, which further understanding of its function may contribute to novel, therapeutic approaches to cancer.
Unlike oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis,' which implies that both alleles that code for a particular gene must be affected before an effect is manifested.
This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein. However, there are cases where mutations in only one allele will cause an effect. A notable example is the gene that codes for p53.
The gene, BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines and previous research has already identified defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression
"Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability," said senior author Shiaw-Yih Lin, assistant professor in the Department of Molecular Therapeutics at M. D. Anderson.
In a series of laboratory experiments, Lin and colleagues show that BRIT1 activates two of these checkpoint pathways.
The ATM pathway springs into action in response to damage caused by ionising radiation. The ATR pathway responds to DNA damage caused by ultraviolet radiation.
By using small interfering RNA (siRNA) to silence the BRIT1 gene, the scientists shut down both checkpoint pathways in cells exposed to either type of radiation.
Researchers then used siRNA to silence the gene in normal human mammary epithelial cells (HMEC).
The results demonstrated that inactivation of the gene caused chromosomal aberrations in 21.2 to 25.6 per cent of cells.
Control group HMEC had no cells with chromosomal aberrations. In cells with the gene silenced that were then exposed to ionising radiation, 80 per cent of cells had chromosomal aberrations.
"We also found that BRIT1 expression is aberrant in several forms of human cancer," Lin said.
The team found reduced expression of the gene in 35 of 87 cases of advanced epithelial ovarian cancer. They also found reduced expression in breast and prostate cancer tissue compared with non-cancerous cells.
A signalling network of molecular checkpoint pathways protects the human genome by detecting DNA damage, initiating repair and halting division of the damaged cell so that it does not replicate.
Genetic analysis of breast cancer specimens revealed a truncated, dysfunctional version of the BRIT1 protein in one sample.
Loss of the DNA damage checkpoint function and the ability to proliferate indefinitely are two cellular changes required for the development of cancer. Lin and colleagues have now tied the gene to both factors.
They previously identified BRIT1 as a repressor of hTERT, a protein that when reactivated immortalizes cells, allowing them to multiply indefinitely.
