P53 Mediates Interstitial Cystitis Antiproliferative Factor (APF) Induced Growth Inhibition Of Human Urothelial Cells

Main Category: Urology / Nephrology
Also Included In: Biology / Biochemistry
Article Date: 30 Sep 2007 - 0:00 PDT

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UroToday.com- Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis. APF is detectable in the urine of 95% of IC patients as compared to approximately 9% of controls and is also a low molecular weight glycosylated peptide related to the membrane receptor frizzled 8. Bioactivities attributed to APF include: suppression of urothelial cell proliferation, increases in transcellular permeability, lowering of the expression of proteins that form intercellular functional complexes, and reduction in the production of heparin binding epidermal growth factor like growth factor from urothelial cells. This accumulation in urine of a bioactive factor, capable of altering the behavior of urothelial cells, is consistent with the clinical observation of epithelial thinning and denudation observed in IC bladder tissue.

Kim and colleagues from Boston and Baltimore have attempted to uncover a pathway through which APF signals. In this report, they discuss experiments that show that treatment of normal human urothelial cells and T24 human bladder carcinoma cells with APF increases p53 levels and that experimentally induced changes in p53 levels alter the APF effect on cell growth indicating that p53 is involved in the mechanism of APF induced growth suppression observed in the context of BPS/IC.

APF treatment suppressed cell proliferation by cell cycle arrest of human bladder urothelial cells. p53 levels increased significantly following APF stimulation. p53 down regulation enhanced the suppressive effect of APF on cell growth. Over expression of p53 itself induced cell cycle arrest in the absence of APF, taken together these observations indicate that p53 can function as a cell cycle regulator of human urothelial cells of bladder origin.

The authors conclude that the data suggest the possibility of targeting p53 or the p53 signaling network proteins as a means of abrogating the pathologic effects of urinary APF and new options for therapeutic intervention in IC seen clinically.

Kim J, Keay SK, Dimitrakov, JD and Freeman MR

Federation of European Biochemical Societies Letters. 581(20):3795-3799, August 2007

Reported by UroToday.com Contributing Editor Philip M Hanno, M.D

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