[Cyclooxygenase 2 and carcinogenesis].
The membrane glycoprotein Cox2 is regulated at transcriptional and post-transcriptional levels by pro-inflammatory agents, cytokines, growth factors, oncogenes, and tumor-promoters. Cox2 is expressed during early stages of colorectal carcinogenesis from the premalignant adenoma stage, and adenocarcinomas of stomach, colon, breast, lung and prostate. Its expression is detected in neoplastic, inflammatory, endothelial and stromal cells. Cox2 is involved in the conversion of arachidonic acid into prostaglandins and thromboxanes, as well as the synthesis of malonaldehyde (MDA, a mutagen) and the production of hydrogen peroxide, which promotes carcinogenesis. The Cox2 products act in turn on serpentine receptors coupled to heterotrimeric G-proteins (R-TXA2, R-PG) that are connected to signaling elements implicated in oncogenesis. Thus, Cox2 plays a key role in early stages of carcinogenesis by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis. tumor cell invasion and setting up of the metastatic process. These mechanisms establish the rationale behind the therapeutic targeting of Cox2 in human solid tumors.
Rodrigues
Sylvie
S
Inserm U482, Signalisation et fonctions cellulaires: applications au diabète et aux cancers digestifs, Hôpital Saint-Antoine, 75571 Paris Cedex 12.
Bruyneel
Erik
E
Rodrigue
Christelle M
CM
Shahin
Emami
E
Gespach
Christian
C
D002454:Cell Differentiation; D002455:Cell Division; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases