Send to

Choose Destination
See comment in PubMed Commons below
Biochim Biophys Acta. 2005 May 25;1729(1):41-9. Epub 2005 Mar 23.

MAPK pathway contributes to density- and hypoxia-induced expression of the tumor-associated carbonic anhydrase IX.

Author information

  • 1Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia.


Transcription of the CA9 gene coding for a tumor-associated carbonic anhydrase IX (CA IX) isoform is regulated by hypoxia via the hypoxia-inducible factor 1 (HIF-1) and by high cell density via the phosphatidylinositol-3-kinase (PI3K) pathway. We examined the role of the mitogen-activated protein kinase (MAPK) pathway in the control of CA9 gene expression. Inhibition of MAPK signaling by U0126 in HeLa cells led to reduced activity of the PR1-HRE-luc CA9 promoter construct and decreased CA IX protein levels in dense culture as well as in hypoxia. Similar reduction was obtained by expression of a dominant-negative ERK1 mutant and was also observed in U0126-treated HIF-1alpha-deficient Ka13 cells. Simultaneous treatment with the MAPK and PI3K inhibitors U0126 and LY 294002 had stronger effect than individual inhibition of these pathways. Taken together, our results suggest that besides the PI3K pathway, the MAPK cascade is involved in the regulation of CA9 gene expression under both hypoxia and high cell density.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center