growth of peripheral and central nervous system tumors is supported by cytoplasmic c-fos in humans and mice周边和中枢神经系统肿瘤的增长是由细胞质c-fos在人类和老鼠.pdfVIP

Growth of Peripheral and Central Nervous System Tumors Is Supported by Cytoplasmic c-Fos in Humans and Mice ¤a ´ ¤b ´ ¤c ¤d David C. Silvestre , German A. Gil , Nicolas Tomasini , Daniela F. Bussolino , Beatriz L. Caputto* ´ ´ ´ ´ ´ Departamento de Quımica Biologica, Facultad de Ciencias Quımicas, CIQUIBIC, Universidad Nacional de Cordoba, Cordoba, Argentina Abstract 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). Principal Findings: 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(2/ 2) 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. Citation: Si