title: The tumor gene survivin is highly expressed in adult renal tubular cells: implications for a pathophysiological role in the kidney.
abstract: The inhibitor of apoptosis protein survivin is of critical importance for regulation of cellular division and survival. Published data point to a restricted function of survivin in embryonic development and cancer; thus survivin has been broadly proposed as an ideal molecular target for specific anti-cancer therapy. In contrast to this paradigm, we report here broad expression of survivin in adult differentiated tissues, as demonstrated at the mRNA and protein levels. Focusing on the kidney, survivin is strongly expressed in proximal tubuli, particularly at the apical membrane, which can be verified in rat, mouse, and human kidneys. In the latter, survivin expression seems to be even stronger in proximal tubuli than in adjacent cancerous tissue. Primary and immortalized human renal tubular cells also showed high levels of survivin protein expression, and RNA interference resulted in a partial G(2)/M arrest of the cell cycle and increased rate of apoptosis. In conclusion, survivin may be of importance for renal pathophysiology and pathology. The predominant apical expression of survivin may indicate a further, yet unknown, function. Interventional strategies to inhibit survivin's function in malignancy need to be carefully (re)evaluated for renal side effects, as well as for other possible organ dysfunctions.
authors.affiliation: Interdisciplinary Center for Clinical Research, Friedrich-Alexander University Erlangen-Nuremberg, Nuremberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lechler
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.forename: Wanja
authors.initials: W
authors.lastname: Bernhardt
authors.forename: Valentina
authors.initials: V
authors.lastname: Campean
authors.forename: Susanne
authors.initials: S
authors.lastname: Gastiger
authors.forename: Thomas
authors.initials: T
authors.lastname: Hackenbeck
authors.forename: Bernd
authors.initials: B
authors.lastname: Klanke
authors.forename: Alexander
authors.initials: A
authors.lastname: Weidemann
authors.forename: Christina
authors.initials: C
authors.lastname: Warnecke
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Dirk
authors.initials: D
authors.lastname: Engehausen
authors.forename: Carsten
authors.initials: C
authors.lastname: Willam
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.forename: Michael Sean
authors.initials: MS
authors.lastname: Wiesener
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; C516989:Birc5 protein, rat; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000077022:Survivin