The tumor gene survivin is highly expressed in adult renal tubular cells: implications for a pathophysiological role in the kidney.
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.
Lechler
Philipp
P
Interdisciplinary Center for Clinical Research, Friedrich-Alexander University Erlangen-Nuremberg, Nuremberg, Germany.
Wu
Xiaoqing
X
Bernhardt
Wanja
W
Campean
Valentina
V
Gastiger
Susanne
S
Hackenbeck
Thomas
T
Klanke
Bernd
B
Weidemann
Alexander
A
Warnecke
Christina
C
Amann
Kerstin
K
Engehausen
Dirk
D
Willam
Carsten
C
Eckardt
Kai-Uwe
KU
Rödel
Franz
F
Wiesener
Michael Sean
MS
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
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