Post-transcriptional regulation of COX2 in tumor cells

November 28, 2001

Cyclooxygenase-2 (COX-2), which acts in many pathological states as the rate limiting enzyme in prostaglandins biosynthesis, is proposed to promote tumor progression at several stages. Prostaglandins apparently not only drive the initial formation of certain pre-cancerous lesions, but also support the development of blood vessels that permit tumor growth and the phenotypic changes that result in metastasis. Much of the analysis of COX-2 regulation has focused on transcriptional control, but Dixon and coworkers now show that post-transcriptional effects may be equally important. The COX-2 mRNA, like other gene products that require rapid induction and repression, carries an A/U-rich element (ARE), a cis-acting RNA-destabilizing sequence. Dixon et al. compared the expression of this mRNA in two different human colon carcinoma cell lines, and they report here that the more aggressively tumorigenic line, HT29, expresses greatly elevated levels of the COX-2 message relative to the slower growing LoVo cell line. This difference can be ascribed to an increase in mRNA stability, not an increase in transcription rate; on the contrary, the COX2 promoter is far more active in the cells with low steady-state levels of COX-2 mRNA. Dixon et al. attribute the specific stabilization of the message to the expression of the RNA-binding protein HuR, which interacts specifically with AREs of the type found in the COX-2 sequence. Overexpression of HuR in LoVo cells increases COX2 mRNA levels as well as increasing the synthesis of prostaglandins and two pro-angiogenic factors whose expression is associated with COX activity. This work suggests the interesting possibility that activation of HuR or other specific regulators of mRNA decay occurs during multistage tumorigenesis.

JCI Journals

Related Blood Vessels Articles from Brightsurf:

Biofriendly protocells pump up blood vessels
In a new study published today in Nature Chemistry, Professor Stephen Mann and Dr Mei Li from Bristol's School of Chemistry, together with Associate Professor Jianbo Liu and colleagues at Hunan University and Central South University in China, prepared synthetic protocells coated in red blood cell fragments for use as nitric oxide generating bio-bots within blood vessels.

Specific and rapid expansion of blood vessels
Upon a heart infarct or stroke, rapid restoration of blood flow, and oxygen delivery to the hypo perfused regions is of eminent importance to prevent further damage to heart or brain.

Flexible and biodegradable electronic blood vessels
Researchers in China and Switzerland have developed electronic blood vessels that can be actively tuned to address subtle changes in the body after implantation.

Lumpy proteins stiffen blood vessels of the brain
Deposits of a protein called ''Medin'', which manifest in virtually all older adults, reduce the elasticity of blood vessels during aging and hence may be a risk factor for vascular dementia.

Cancer cells take over blood vessels to spread
In laboratory studies, Johns Hopkins Kimmel Cancer Center and Johns Hopkins University researchers observed a key step in how cancer cells may spread from a primary tumor to a distant site within the body, a process known as metastasis.

Novel function of platelets in tumor blood vessels found
Scientists at Uppsala University have discovered a hitherto unknown function of blood platelets in cancer.

Blood vessels can make you fat, and yet fit
IBS scientists have reported Angiopoietin-2 (Angpt2) as a key driver that inhibits the accumulation of potbellies by enabling the proper transport of fatty acid into general circulation in blood vessels, thus preventing insulin resistance.

Brothers in arms: The brain and its blood vessels
The brain and its surrounding blood vessels exist in a close relationship.

Feeling the pressure: How blood vessels sense their environment
Researchers from the University of Tsukuba discovered that Thbs1 is a key extracellular mediator of mechanotransduction upon mechanical stress.

Human textiles to repair blood vessels
As the leading cause of mortality worldwide, cardiovascular diseases claim over 17 million lives each year, according to World Health Organization estimates.

Read More: Blood Vessels News and Blood Vessels Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to