Stem cell and Molecular Biology laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036, India.
Gene. 2013 Sep 25;527(2):521-8. doi: 10.1016/j.gene.2013.06.051. Epub 2013 Jul 9.
Fanconi anemia (FA) is a genetic disorder characterized by progressive bone marrow failure and a predisposition to cancers like acute myeloid leukemia, lung and squamous cell carcinomas. DNA damage in a healthy cell activates the FA pathway where 15 individual FA proteins interact and function together to maintain genomic stability. The disruption of this pathway results in the characteristic cellular phenotype and clinical outcome of the disease. The diverse clinical symptoms of FA such as impaired immunity and predisposition to cancers may not be explained exclusively by a non-functional FA pathway. These symptoms could then be attributed to defects in other functions of the individual FA proteins. To identify the effects of a mutant FA protein, FANCC, a transcriptome analysis was carried out on a FANCC mutant cell line (EUFA 450) and its revertant isogenic control cell line (EUFA 450Rev). Microarray data revealed dysregulation of genes involved in regulation of cell death and immune response. This study reports for the first time, the lowered expression of a tumor suppressor gene - caveolin-1, in FANCC mutant cells. The downregulation of caveolin-1 can be significant as Fanconi anemia patients have an elevated predisposition to develop cancer.
范可尼贫血症（FA）是一种遗传性疾病，其特征是骨髓衰竭进行性发展，以及易患急性髓系白血病、肺癌和鳞状细胞癌等癌症。健康细胞中的 DNA 损伤会激活 FA 途径，其中 15 种不同的 FA 蛋白相互作用并共同发挥作用，以维持基因组稳定性。该途径的破坏会导致疾病的典型细胞表型和临床结果。FA 的多种临床症状，如免疫受损和易患癌症，可能不仅仅是由于 FA 途径功能失调所致。这些症状可能归因于个体 FA 蛋白其他功能的缺陷。为了确定突变 FA 蛋白 FANCC 的影响，对 FANCC 突变细胞系（EUFA 450）及其回复系同基因对照细胞系（EUFA 450Rev）进行了转录组分析。微阵列数据分析显示，参与细胞死亡和免疫反应调节的基因失调。本研究首次报道了 FANCC 突变细胞中肿瘤抑制基因 - 窖蛋白-1 的表达降低。窖蛋白-1 的下调可能非常重要，因为范可尼贫血症患者易患癌症。
