Journal Article


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



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

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