Expression of the urokinase plasminogen activator receptor is transiently required during "priming" of PC12 cells in nerve growth factor-directed cellular differentiation

We previously identified the urokinase plasminogen activator receptor (UPAR ) as a gene induced by nerve growth factor (NGF), but not by epidermal grow th factor (EGF), in PC12 cells (Farias-Eisner et al, [2000] J, Neurosci. 20 :230-239). Antisense oligonucletides for the UPAR mRNA or an antibody direc ted against UPAR protein, added simultaneously with NGF, block NGF-induced morphological and biochemical differentiation of PC12 cells. In this report , we show that anti-UPAR antibody blocks morphological differentiation and the expression of two NGF-specific secondary response genes, collagenase-1 and transin, in PC12 cells only during the first 2 hr following NGF exposur e. These data suggest that induced UPAR expression is required only over a short period of time following exposure to NGF for the differentiation prog ram in PC12 cells to proceed. For two models of "primed" PC12 cells, we fou nd that UPAR expression and function are not required for NGF-induced diffe rentiation. UPAR and the secondary response genes collagenase-1 and transin are not induced in "primed" PC12 cells in response to NGF, and anti-UPAR a ntibody does not block morphological differentiation in these cells. Our da ta suggests that UPAR is required only transiently during the "priming" of PC12 cells in NGF-induced PC12 cell differentiation. (C) 2001 Wiley-Liss, I nc.