Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in a p38-dependent manner.

Abstract

BACKGROUND/AIMS:

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.

CONCLUSION:

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: Lu Tie, Ning Lu, Xue-Yang Pan, Yan Pan, Yu An, Jun-Wei Gao, Yan-Hua Lin, He-Ming Yu, Xue-Jun Li
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 29 Issue 1-2 Pg. 269-80 ( 2012) ISSN: 1421-9778 [Electronic] Germany
• PMID: 22415096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Aquaporin 1
• Cobalt
• Protein Kinase C
• p38 Mitogen-Activated Protein Kinases
• cobaltous chloride
• Calcium

Topics

• Aquaporin 1 (genetics, metabolism)
• Calcium (metabolism)
• Cell Hypoxia
• Cell Line, Tumor
• Cobalt (pharmacology)
• Humans
• Male
• Phosphorylation
• Prostatic Neoplasms (metabolism, pathology)
• Protein Kinase C (metabolism)
• Transcription, Genetic (drug effects)
• Up-Regulation
• p38 Mitogen-Activated Protein Kinases (metabolism)