Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is often assumed that MAPK pathways drive proliferation of normal uroepithelial (UEC) and urothelial carcinoma (TCC) cells. To check this assumption, activities and inducibilities of promoters containing serum-response elements (SRE) or AP-1 binding sites were investigated in cultured UEC and seven TCC lines. Reporter plasmids dependent on SRE or AP-1 sites were highly active in UEC, but significantly less so in TCC lines. Reporter activity in TCC lines could be induced by constitutively active MEKK4 or TPA. Accordingly, phosphorylation of the MAPK pathway components MEK, ERK, and ELK1 was most pronounced in UEC and lower in TCC lines. MAPK-dependent promoter activities and bromodeoxyuridine incorporation decreased in UEC upon withdrawal of growth factors, but less so in TCC lines, in which serum diminution increased apoptosis. Likewise, E2F-dependent promoters responded to growth factors in UEC, but were more serum-independent in the TCC lines, which lack either RB1 or p16(INK4A). MEK inhibitors inhibited BrdU incorporation in UEC more strongly than in TCC lines. Thus, proliferation of normal uroepithelial cells is indeed associated with activation of MAPK pathways. However, autonomous proliferation of TCC lines--unexpectedly--appears much less dependent on MAPK activation and may rather be promoted by defects in cell cycle regulation.
 ...
PMID:Activities of MAP-kinase pathways in normal uroepithelial cells and urothelial carcinoma cell lines. 1249 Jan 93

TERE1/UBIAD1 is involved in SCCD (Schnyder crystalline corneal dystrophy) and multiple human cancers. So far, the molecular mechanism of TERE1/UBIAD1 in tumourigenesis is unclear. Here, the expression levels of hTERT and TERE1/UBIAD1 in pathologically proven Chinese TCC (transitional cell carcinoma) samples were measured. It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling. Chemically modified TERE1 siRNA oligos were used to knock down TERE1 expression in human L02 cells. Cells transfected with TERE1 siRNA oligos underwent significant cell proliferation. When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling. Addition of the MEK inhibitor U0126 into the transfected L02 cells described above inhibited ERK phosphorylation and hTERT expression. Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation. TERE1 might be a new negative regulator of Ras-MAPK signalling, which plays a pivotal role in the cell proliferation of multiple human cancers.
 ...
PMID:Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation. 2311 42