Lin Zong-Shin, Chung Chiao-Chen, Liu Yu-Chia, Chen Tsung-Ming, Yu Yung-Luen, Wang Shao-Chun, Chen Ya-Huey
Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University Taichung 40402, Taiwan.
Center for Molecular Medicine, China Medical University Hospital Taichung 40447, Taiwan.
Am J Cancer Res. 2018 Oct 1;8(10):1989-2004. eCollection 2018.
Chondrosarcoma is a malignant and common bone tumor that is highly resistant to radiation and chemotherapy. At this moment, amputation surgery is the only option which unfortunately has serious impact to daily lives of the patients. Thus, there is an urgent need to understand causative molecular mechanisms underlying the disease for more accurate prognosis and more effective targeted treatment. In the current study, we identify the transcription factor FOXA1 through cDNA microarray screening comparing normal versus chondrosarcoma cells and investigate the mechanisms underlying its function in chondrosarcoma development. We show that FOXA1 enhances expression of the cyclin B1 gene, which in turn drives cell cycle progression through G2-M transition thus promotes cell cycle progression of chondrosarcoma cells.
软骨肉瘤是一种常见的恶性骨肿瘤，对放疗和化疗具有高度抗性。目前，截肢手术是唯一的选择，但不幸的是，这对患者的日常生活有严重影响。因此，迫切需要了解该疾病潜在的致病分子机制，以实现更准确的预后和更有效的靶向治疗。在本研究中，我们通过比较正常细胞与软骨肉瘤细胞的cDNA微阵列筛选，鉴定出转录因子FOXA1，并研究其在软骨肉瘤发生发展中发挥作用的机制。我们发现，FOXA1增强了细胞周期蛋白B1基因的表达，进而通过G2-M期转换驱动细胞周期进程，从而促进软骨肉瘤细胞的细胞周期进程。
