2 TYPES OF AMYLOID PRECURSOR PROTEIN (APP) MESSENGER-RNA IN RAT GLIOMA CELL-LINES - UP-REGULATION VIA A CYCLIC-AMP-DEPENDENT PATHWAY

APP is a multifunctional transmembrane glycoprotein and the only known natural source of beta A4 peptide-the major constituent of senile pla ques in Alzheimer's disease (AD). The expression and cAMP-dependent re gulation of the APP gene were investigated in primary cultures of rat astrocytes and two related glioma cell lines, BT4C and BT4Cn, which ex hibit distinct invasive phenotypes. Besides the well-characterized 3.5 kb APP mRNA class, a robust expression of an unusual 2.8 kb APP mRNA class was revealed by Northern blotting in bath glioma cell lines, but not in the astrocytes. Low amounts of the 2.8 kb APP mRNA species wer e also observed in rat liver and occasionally in aged rat brain. The 2 .8 kb APP mRNA contained exons 1-18 and may thus be generated by trunc ation of the 3' untranslated region. For the first time, regulation of the APP gene via a cAMP-dependent mechanism was shown. Exposure to dB cAMP dramatically upregulated the 3.5 and 2.8 kb transcripts in BT4C c ells, and, to a lesser extent, in BT4Cn cells where the constitutive e xpression of the APP gene was much higher. Elucidation of the factors involved in cAMP-dependent induction of APP mRNA in these cells may sh ed more light on the molecular mechanisms of APP overexpression.