Viral Kirsten ras infection differentiates PC12 cells and enhances their survival upon implantation into brain.
Neuronal cells from established cell lines can offer a well-characterized source of cells for transplantation to the brain that is an alternative to fetal neurons. The infection of members of the PC12 cell line with a retrovirus containing ras-oncogene leads to their neuronal differentiation without the need of nerve growth factor (NGF). We find that neoplastic, naive PC12 cells grafted to the striatum of normal adult rats cause the transient formation of large hemorrhagic cavities and do not survive. After differentiation by infection with Kirsten-ras murine sarcoma virus, and transplantation to the opposite striatum of the same brain, PC12 cells survive for at least 8 weeks and emit neurites. These neuron-like cells and their neurites retain tyrosine hydroxylase and choline acetyl transferase, as detected immunohistochemically. Thus, ras-primed PC12 cells may serve as a continuous source for both cholinergic and adrenergic transmitters, in vivo, without the need of exogenous nerve growth factor.
Laboratory of Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892.
O
O
Okuda
J
J
Bressler
L
L
Chang
M
M
Brightman
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D011905:Genes, ras / Q000502:physiology*; D007708:Kirsten murine sarcoma virus; D016716:PC12 Cells / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D012513:Sarcoma, Experimental / Q000503:physiopathology*