Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts

Abstract

Fibroblasts that harbor an antisense construct of amyloid beta protein precursor (ABPP) cDNA, A-1, produced less ABPP mRNA and ABPP and grew poorly. Normal growth was restored when either parent cell conditioned medium (CM) or purified ABPP was provided. The capacity of the CM to restore cell growth was abolished by passage through an anti-ABPP immunoaffinity column; the activity was in the bound fraction. A Mr 90,000 protein recognized by the anti-ABPP antibody was diminished in the CM of A-1. CM from ABPP cDNA-transfected cells expressing high levels of ABPP was more potent than that from non-transfected parent cells in restoring A-1 growth. These results indicate that ABPP is released from cells into the medium and has an autocrine function in growth regulation.