Growth of peripheral and central nervous system tumors is supported by cytoplasmic c-Fos in humans and mice.
BACKGROUND
We have previously shown that the transcription factor c-Fos is also capable of associating to endoplasmic reticulum membranes (ER) and activating phospholipid synthesis. Herein we examined phospholipid synthesis status in brain tumors from human patients and from NPcis mice, an animal model of the human disease Neurofibromatosis Type 1 (NF1).


RESULTS
In human samples, c-Fos expression was at the limit of detection in non-pathological specimens, but was abundantly expressed associated to ER membranes in tumor cells. This was also observed in CNS of adult tumor-bearing NPcis mice but not in NPcis fos(-/-) KO mice. A glioblastoma multiforme and a malignant PNS tumor from a NF1 patient (MPNST) showed a 2- and 4- fold c-Fos-dependent phospholipid synthesis activation, respectively. MPNST samples also showed increased cell proliferation rates and abundant c-Fos expression.


CONCLUSIONS
Results highlight a role of cytoplasmic c-Fos as an activator of phospholipid synthesis in events demanding high rates of membrane biogenesis as occurs for the exacerbated growth of tumors cells. They also disclose this protein as a potential target for controlling tumor growth in the nervous system.
Silvestre
David C
DC
Departamento de Química Biológica, Facultad de Ciencias Químicas, CIQUIBIC, Universidad Nacional de Córdoba, Córdoba, Argentina.
Gil
Germán A
GA
Tomasini
Nicolás
N
Bussolino
Daniela F
DF
Caputto
Beatriz L
BL
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009456:Neurofibromatosis 1 / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*
D016760:Proto-Oncogene Proteins c-fos