Cover: Polycystin-2 staining of MDCK cells
Polycystins: Multi-purpose Cellular Tools?
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnifi cus Dr.D.D.Breimer,
hoogleraar in de faculteit der Wiskunde en Natuurwetenschappen en die der Geneeskunde,
volgens besluit van het College voor Promoties te verdedigen op donderdag 14 september 2006
klokke 16.15 uur door Ngoc Hang Le
geboren te Vinh Long (Vietnam)
in 1978
Promotiecommissie
Promotor: Prof. dr. M.H. Breuning
Co-promotor: Dr. D.J.M. Peters
Referent: Dr. A.C.M. Ong (Sheffi eld University, UK)
Overige leden: Dr. ir. J.A.F. van Dam Prof. dr. G.J. van Ommen
Prof. dr. R. Fodde (Erasmus MC, Rotterdam)
Contents
Chapter 1. Introduction 9
Outline of thesis 26
Chapter 2. Aberrant Polycystin-1 Expression results in 31
Modifi cation of AP-1 Activity, whereas Wnt Signaling remains unaffected Chapter 3. Increased Activity of the Activator Protein-1 49
Transcription Factor Components ATF2, c-Jun, and c-Fos in human and mouse Autosomal Dominant Polycystic Kidney Disease Chapter 4. Impaired ERK Signaling Activity in human and 65
mouse renal cystic epithelial Cells Chapter 5. Down-regulation of PKD1 and PKD2 after 77
DNA Damage Chapter 6. Murine Models for Polycystic Kidney Disease 87
Towards Therapeutic Intervention Strategies 96
for Polycystic Kidney Disease Chapter 7. Summary and Discussion 105
Nederlandse Samenvatting 109
Curriculum Vitae 110
List of publications 111
Nawoord 113
