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2010 ; 14
(4
): 758-70
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The role of HIF prolyl hydroxylases in tumour growth
#MMPMID20178464
Jokilehto T
; Jaakkola PM
J Cell Mol Med
2010[Apr]; 14
(4
): 758-70
PMID20178464
show ga
Tumour hypoxia is a well-known microenvironmental factor that causes cancer
progression and resistance to cancer treatment. This involves multiple mechanisms
of which the best-understood ones are mediated through transcriptional gene
activation by the hypoxia-inducible factors (HIFs). HIFs in turn are regulated in
response to oxygen availability by a family of iron- and 2-oxoglutarate-dependent
dioxygenases, the HIF prolyl hydroxylases (PHDs). PHDs inactivate HIFs in
normoxia by activating degradation of the HIF-alpha subunit but release HIF
activation in poorly oxygenated conditions. The function of HIF in tumours is
fairly well characterized but our understanding on the outcome of PHDs in tumours
is much more limited. Here we review the function of PHDs on the HIF system, the
expression of PHDs in human tumours as well as their putative function in cancer.
The PHDs may have either tumour promoting or suppressing activity. Their outcome
in cancer depends on the cell and cancer type-specific expression and on the
availability of diverse natural PHD inhibitors in tumours. Moreover, besides the
action of PHDs on HIF, recent data suggest PHD function in non-HIF signalling.
Together the data illustrate a complex operation of the oxygen sensors in cancer.
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