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 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.
Adiseshaiah
Pavan
P
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Lindner
Daniel J
DJ
Kalvakolanu
Dhananjaya V
DV
Reddy
Sekhar P
SP
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004847:Epithelial Cells; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000737:chemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism* / Q000502:physiology*; D000099169:Fos-Related Antigen 1
D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1; C000715470:MAS1 protein, human; C059485:matrigel