Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells

The major form of autosomal dominant polycystic kidney disease (ADPKD) resu lts from mutation of a gene (PKD1) of unknown function that is essential fo r the later stages of renal tubular differentiation. In this report, we des cribe a novel cell culture system for studying how PKD1 regulates this proc ess. We show that expression of human PKD1 in MDCK cells slows their growth and protects them from programmed cell death. MDCK cells expressing PKD1 a lso spontaneously form branching tubules while control cells form simple cy sts. Increased cell proliferation and apoptosis have been implicated in the pathogenesis of cystic diseases. Our study suggests that PKD1 may function to regulate both pathways, allowing cells to enter a differentiation pathw ay that results in tubule formation.