p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells.
Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis, a urinary bladder disorder of unknown etiology that is characterized by chronic pelvic pain. The present study was directed toward uncovering a pathway through which APF signals. Treatment of human urothelial cells with native APF resulted in growth inhibition accompanied by blockade of cell cycle transit and increased p53. Reduced expression of p53 by RNA interference diminished, while ectopic expression of p53 mimicked, the effects of APF. These are the first findings implicating the network of p53 target genes in urothelial defects associated with interstitial cystitis.
Kim
Jayoung
J
The Urological Diseases Research Center, Children's Hospital Boston, Boston, MA 02115, USA.
Keay
Susan K
SK
Dimitrakov
Jordan D
JD
Freeman
Michael R
MR
D002277:Carcinoma / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018856:Cystitis, Interstitial / Q000503:physiopathology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D019459:Urothelium / Q000187:drug effects*
D006023:Glycoproteins; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C490708:antiproliferative factor APF, human