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(American Journal of Pathology. 2007;171:1483-1498.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070132

The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells

Implications for a Pathophysiological Role in the Kidney

Philipp Lechler*, Xiaoqing Wu*, Wanja Bernhardt{dagger}, Valentina Campean{ddagger}, Susanne Gastiger*{dagger}, Thomas Hackenbeck*{dagger}, Bernd Klanke{dagger}, Alexander Weidemann{dagger}, Christina Warnecke{dagger}, Kerstin Amann{ddagger}, Dirk Engehausen§, Carsten Willam{dagger}, Kai-Uwe Eckardt{dagger}, Franz Rödel and Michael Sean Wiesener*{dagger}

From the Interdisciplinary Center for Clinical Research,* and the Departments of Nephrology and Hypertension,{dagger} Pathology,{ddagger} and Urology,§ Friedrich-Alexander University Erlangen-Nuremberg, Nuremberg; and the Department of Radiation Therapy and Oncology, Johann-Wolfgang-Goethe University Frankfurt, Frankfurt, Germany

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 G2/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.




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