Department of Molecular Oncology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Int J Cancer. 2012 Jun 1;130(11):2549-56. doi: 10.1002/ijc.26259. Epub 2011 Aug 16.
Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10(-4) ) and the differentiation of the tumor (p = 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.
四和半 Lin-11、Isl-1、Mac-3（LIM）蛋白 1（FHL1）与致癌作用有关。然而，FHL1 在肺癌中的作用尚不清楚，其肿瘤抑制作用的详细机制也知之甚少。本研究旨在检测肺癌患者中 FHL1 的表达，并探讨其与肺癌细胞生长的关系。免疫印迹和免疫组织化学显示，超过 90%的 80 例肺癌患者中 FHL1 蛋白下调。FHL1 的表达与肿瘤组织学类型（p < 10(-4)）和肿瘤的分化强烈相关（p = 0.002）。FHL1 抑制人肺癌细胞系的锚定依赖性和非依赖性生长。FHL1 对肺癌细胞生长的抑制作用与 G1 和 G2/M 细胞周期阻滞相关，同时明显抑制细胞周期蛋白 A、B1 和 D，诱导细胞周期蛋白依赖性激酶抑制剂 p21（WAF1/CIP1）和 p27（Kip1）。直接向肿瘤内注射表达 FHL1 的腺病毒显著抑制了裸鼠 A549 肺癌细胞的生长。我们的数据表明，FHL1 的表达降低可能在肺癌的发生和发展中起重要作用，FHL1 可能是肺癌基因治疗的一个有用靶点。
