Type

Journal Article

Authors

D J Fitzgerald
F E Murray
E W Kay
T G Neilan
D M Sadlier
G M Scully
S C Austin
S M Byrne
G A Doherty

Subjects

Biochemistry

Topics
oligonucleotide array sequence analysis rna interference protein serine threonine kinases apoptosis regulatory proteins cell line tumor dinoprostone antagonists inhibitors stk17b protein human pathology ptgs2 protein human humans physiology cyclooxygenase 2 genetics apoptosis metabolism colorectal neoplasms gene expression regulation neoplastic

Regulation of the apoptosis-inducing kinase DRAK2 by cyclooxygenase-2 in colorectal cancer. (2009)

Abstract Cyclooxygenase-2 (COX-2) is over-expressed in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis. Selective COX-2 inhibition is effective in CRC prevention, although having adverse cardiovascular effects, thus focus has shifted to downstream pathways. Microarray experiments identified genes regulated by COX-2 in HCA7 CRC cells. In vitro and in vivo regulation of DRAK2 (DAP kinase-related apoptosis-inducing kinase 2 or STK17beta, an apoptosis-inducing kinase) by COX-2 was validated by qRT-PCR. Inhibition of COX-2 induced apoptosis and enhanced DRAK2 expression in HCA7 cells (4.4-fold increase at 4 h by qRT-PCR, P=0.001), an effect prevented by co-administration of PGE(2). DRAK2 levels were suppressed in a panel of human colorectal tumours (n=10) compared to normal mucosa, and showed inverse correlation with COX-2 expression (R=-0.68, R2=0.46, P=0.03). Administration of the selective COX-2 inhibitor rofecoxib to patients with CRC (n=5) induced DRAK2 expression in tumours (2.5-fold increase, P=0.01). In vitro silencing of DRAK2 by RNAi enhanced CRC cell survival following COX-2 inhibitor treatment. DRAK2 is a serine-threonine kinase implicated in the regulation of apoptosis and is negatively regulated by COX-2 in vitro and in vivo, suggesting a novel mechanism for the effect of COX-2 on cancer cell survival.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

D J Fitzgerald, F E Murray, E W Kay, T G Neilan, D M Sadlier, G M Scully, S C Austin, S M Byrne, G A Doherty

Experts in our system

1
D J Fitzgerald
Royal College of Surgeons in Ireland
Total Publications: 101
 
2
F E Murray
Royal College of Surgeons in Ireland
 
3
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
4
Susan Byrne
Trinity College Dublin
Total Publications: 18
 
5
Glen A Doherty
University College Dublin
Total Publications: 57