Relative resistance of SGK1 knockout mice against chemical carcinogenesis.
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Relative resistance of SGK1 knockout mice against chemical carcinogenesis. / Nasir, Omaima; Wang, Kan; Föller, Michael; Gu, Shuchen; Bhandaru, Madhuri; Ackermann, Teresa F; Boini, Krishna M; Mack, Andreas; Klingel, Karin; Amato, Rosario; Perrotti, Nicola; Kuhl, Dietmar; Behrens, Jürgen; Stournaras, Christos; Lang, Florian.
in: IUBMB LIFE, Jahrgang 61, Nr. 7, 7, 2009, S. 768-776.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Relative resistance of SGK1 knockout mice against chemical carcinogenesis.
AU - Nasir, Omaima
AU - Wang, Kan
AU - Föller, Michael
AU - Gu, Shuchen
AU - Bhandaru, Madhuri
AU - Ackermann, Teresa F
AU - Boini, Krishna M
AU - Mack, Andreas
AU - Klingel, Karin
AU - Amato, Rosario
AU - Perrotti, Nicola
AU - Kuhl, Dietmar
AU - Behrens, Jürgen
AU - Stournaras, Christos
AU - Lang, Florian
PY - 2009
Y1 - 2009
N2 - The serum and glucocorticoid inducible kinase SGK1 was originally cloned from mammary tumor cells. SGK1 was found to be up-regulated in a variety of tumors, but down-regulated in several distinct tumors. Thus, evidence for a role of SGK1 in tumor growth remained conflicting. According to in vitro observations, SGK1 is up-regulated by the oncogene beta-catenin and negatively regulates the proapoptotic transcription factor FOXO3a, which in turn stimulates transcription of the Bcl2-interacting mediator BIM. This study aimed to define the role of SGK1 in colon carcinoma in vivo. SGK1 knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) were subjected to chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium for 7 days). Moreover, SGK1 was silenced in HEK293 cells. FOXO3a and BIM protein abundance was determined by Western blotting and immunohistochemistry. Following chemical cancerogenesis, sgk1(-/-)mice developed significantly less colonic tumors than sgk1(+/+)mice. According to Western blotting and immunohistochemistry, SGK1 deficiency enhanced the expression of FOXO3a and BIM both, in vitro and in vivo. SGK1 deficiency counteracts the development of colonic tumors, an effect at least in part due to up-regulation of FOXO3a and BIM.
AB - The serum and glucocorticoid inducible kinase SGK1 was originally cloned from mammary tumor cells. SGK1 was found to be up-regulated in a variety of tumors, but down-regulated in several distinct tumors. Thus, evidence for a role of SGK1 in tumor growth remained conflicting. According to in vitro observations, SGK1 is up-regulated by the oncogene beta-catenin and negatively regulates the proapoptotic transcription factor FOXO3a, which in turn stimulates transcription of the Bcl2-interacting mediator BIM. This study aimed to define the role of SGK1 in colon carcinoma in vivo. SGK1 knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) were subjected to chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium for 7 days). Moreover, SGK1 was silenced in HEK293 cells. FOXO3a and BIM protein abundance was determined by Western blotting and immunohistochemistry. Following chemical cancerogenesis, sgk1(-/-)mice developed significantly less colonic tumors than sgk1(+/+)mice. According to Western blotting and immunohistochemistry, SGK1 deficiency enhanced the expression of FOXO3a and BIM both, in vitro and in vivo. SGK1 deficiency counteracts the development of colonic tumors, an effect at least in part due to up-regulation of FOXO3a and BIM.
M3 - SCORING: Zeitschriftenaufsatz
VL - 61
SP - 768
EP - 776
IS - 7
M1 - 7
ER -
