Aberrant expression of the COX2/PGE₂ axis is induced by activation of the RAF/MEK/ERK pathway in BRAF^V595E canine urothelial carcinoma.

ABSTRACT: Cancer-promoting inflammation is an important event in cancer development. Canine urothelial carcinoma (cUC) overexpresses prostaglandin E₂ (PGE₂) and has a unique sensitivity to cyclooxygenase 2 (COX2)-inhibiting therapy. In addition, majority of cUC harbour BRAF^V595E mutation. However, mechanisms underlying aberrant PGE₂ production in BRAF^V595E cUC patients remain unclear. Drug screening revealed that inhibition of RAF/MEK/ERK pathway, p38 and JNK pathway reduced PGE₂ production in cUC cells. By pharmacological inhibition of the multiple components in the pathway, activation of the ERK MAPK pathway was shown to mediate overexpression of COX2 and production of PGE₂ in BRAF^V595E cUC cells. In silico gai

SUBMITTER: Yoshitake R 

PROVIDER: S-EPMC7210937 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature