FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo
FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo
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DOI：
10.1158/0008-5472.can-06-4687
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发表时间：
2007-07-01
期刊：
影响因子：
11.2
通讯作者：
Reddy, Sekhar P.
中科院分区：
文献类型：
--
作者：
Adiseshaiah, Pavan;Lindner, Daniel J.;Reddy, Sekhar P.
FRA-1与JUN家族成员形成激活蛋白-1复合物并驱动基因转录。FRA-1与气道鳞状上皮化生的发展有关，并且在食管和胃的鳞状细胞癌中经常过表达。我们和其他人已经证明了肺致癌物（如香烟烟雾和石棉）在肺上皮细胞中对FRA-1的高水平持续诱导。然而，FRA-1在调节肺上皮细胞生长和侵袭中的确切作用知之甚少。为了研究这一方面，我们已经稳定过表达FRA-1在人类II型样肺泡恶性细胞系（A549）和非恶性支气管上皮细胞系（BEAS-2B）。FRA-1显著增强A549和BEAS-2B细胞的增殖、运动和侵袭速率。在无胸腺裸鼠中，FRA-1，而不是对照载体，迅速增强A549细胞的肿瘤形成和转移。相反，FRA-1未能促进BEAS-2B的肿瘤形成。我们认为，FRA-1可以促进运动，入侵，和锚定非依赖性生长的肺上皮细胞在体外，但对肿瘤的形成是不够的。
FRA-1 forms activator protein-1 complexes in association with members of the JUN family and drives gene transcription. FRA-1 has been implicated in the development of airway squamous metaplasia and is frequently overexpressed in squamous cell carcinomas of the esophagus and stomach. We and others have shown a high level of persistent induction of FRA-1 by lung carcinogens, such as cigarette smoke and asbestos, in pulmonary epithelial cells. However, the exact roles of FRA-1 in regulating lung epithelial cell growth and invasion are poorly understood. To examine this aspect, we have stably overexpressed FRA-1 in human type-II-like alveolar malignant cell line (A549) and a nonmalignant bronchial epithelial cell line (BEAS-2B). FRA-1 greatly enhanced the rate of proliferation, motility, and invasion of A549 and BEAS-2B cells. In athymic nude mice, FRA-1, but not the control vector, rapidly enhanced tumor formation and metastasis by A549 cells. In contrast, FRA-1 failed to promote tumor formation by BEAS-2B. We suggest that FRA-1 can promote motility, invasion, and anchorage-independent growth of lung epithelial cells in vitro, but is insufficient for tumor formation.