We now show by microarray analysis, luciferase assay, mutagenesis, and chromatin immunoprecipitation that CREB and AP1 contribute to increased expression of the amphiregulin gene, which codifies for an epidermal growth factor-like peptide, in ADPKD cystic cells, thereby promoting their cell growth.
Cyclic AMP and growth factors, including epidermal growth factor, have complementary effects to accelerate the enlargement of ADPKD cysts, and thereby to contribute to the progression of the disease.
In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.
In contrast to NK cells, the growth and propagation of ADPKD cells were not supported by defined medium alone but required serum supplementation and ADPKD cells did not respond to growth factors (insulin, transferrin, EGF) that promoted the growth of NK cells.