title: Overexpression of 17β-hydroxysteroid dehydrogenase type 10 increases pheochromocytoma cell growth and resistance to cell death.
abstract: BACKGROUND
  17β-hydroxysteroid dehydrogenase type 10 (HSD10) has been shown to play a protective role in cells undergoing stress. Upregulation of HSD10 under nutrient-limiting conditions leads to recovery of a homeostatic state. Across disease states, increased HSD10 levels can have a profound and varied impact, such as beneficial in Parkinson's disease and harmful in Alzheimer's disease. Recently, HSD10 overexpression has been observed in some prostate and bone cancers, consistently correlating with poor patient prognosis. As the role of HSD10 in cancer remains underexplored, we propose that cancer cells utilize this enzyme to promote cancer cell survival under cell death conditions.
  
  
  METHODS
  The proliferative effect of HSD10 was examined in transfected pheochromocytoma cells by growth curve analysis and a xenograft model. Fluctuations in mitochondrial bioenergetics were evaluated by electron transport chain complex enzyme activity assays and energy production. Additionally, the effect of HSD10 on pheochromocytoma resistance to cell death was investigated using TUNEL staining, MTT, and complex IV enzyme activity assays.
  
  
  RESULTS
  In this study, we examined the tumor-promoting effect of HSD10 in pheochromocytoma cells. Overexpression of HSD10 increased pheochromocytoma cell growth in both in vitro cell culture and an in vivo xenograft mouse model. The increases in respiratory enzymes and energy generation observed in HSD10-overexpressing cells likely supported the accelerated growth rate observed. Furthermore, cells overexpressing HSD10 were more resistant to oxidative stress-induced perturbation.
  
  
  CONCLUSIONS
  Our findings demonstrate that overexpression of HSD10 accelerates pheochromocytoma cell growth, enhances cell respiration, and increases cellular resistance to cell death induction. This suggests that blockade of HSD10 may halt and/or prevent cancer growth, thus providing a promising novel target for cancer patients as a screening or therapeutic option.
authors: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66047, USA. e086c574@ku.edu.|Higuchi Biosciences Center, University of Kansas, Lawrence, KS, 66047, USA. e086c574@ku.edu.
authors: Emily A
authors: EA
authors: Carlson
authors: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USA. r100m828@ku.edu.
authors: Rebecca T
authors: RT
authors: Marquez
authors: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66047, USA. f756d288@ku.edu.|Higuchi Biosciences Center, University of Kansas, Lawrence, KS, 66047, USA. f756d288@ku.edu.
authors: Fang
authors: F
authors: Du
authors: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66047, USA. yongfuwang@ku.edu.|Higuchi Biosciences Center, University of Kansas, Lawrence, KS, 66047, USA. yongfuwang@ku.edu.
authors: Yongfu
authors: Y
authors: Wang
authors: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USA. xul@ku.edu.
authors: Liang
authors: L
authors: Xu
authors: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66047, USA. shidu@ku.edu.|Higuchi Biosciences Center, University of Kansas, Lawrence, KS, 66047, USA. shidu@ku.edu.
authors: Shirley ShiDu
authors: SS
authors: Yan
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D021983:Cyclophilins / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D014162:Transfection
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; D021983:Cyclophilins