title: Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in a p38-dependent manner.
abstract: OBJECTIVE
  Aquaporin-1 (AQP1) is a glycoprotein that mediates osmotic water transport, its expression has been found to correlate with tumour stage in some tumours. However, the mechanism by which AQP1 protein expression is regulated in tumor cells remains to be fully elucidated. We hypothesized that hypoxia might play an important role in AQP1 induction during tumorigenesis and at the late stages of tumor development.
  
  
  METHODS
  Isotonic and serum-free hypoxic models were used to investigate AQP1 expression in PC-3M human prostate cancer cells.
  
  
  RESULTS
  AQP1 expression was up-regulated by density-induced pericellular hypoxia and cobalt(II) chloride (CoCl(2))-induced hypoxia at the transcriptional level. Moreover, phosphorylation of p38 mitogen-activated protein kinase (MAPK) was induced by density-induced pericellular hypoxia and CoCl(2)-induced hypoxia, specific inhibitors of p38 MAPK could concentration-dependently block those effects of hypoxia on AQP1 expression. Intracellular calcium ion (Ca(2+)) and protein kinase C (PKC) were shown to be responsible for the activation of p38 MAPK pathway. In addition, AQP1 induction in dense cultures was dependent on lowered oxygen (O(2)) tension. In high cell density culture, certain secretory proteins might induce AQP1 expression indirectly.
  
  
  CONCLUSIONS
  These findings suggest that AQP1 could be induced by hypoxia at transcription level, and the regulation of AQP1 in PC-3M cells is dependent on calcium, PKC and p38 MAPK, as well as low oxygen tension.
authors.affiliation: State Key Laboratory of Natural & Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences and Institute of System Biomedicine, Peking University, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Xue-Yang
authors.initials: XY
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Gao
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Lin
authors.forename: He-Ming
authors.initials: HM
authors.lastname: Yu
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051398:Aquaporin 1; D003035:Cobalt; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C018021:cobaltous chloride; D002118:Calcium