Hypomethylation and hypoexpression of human CYP2E1 gene in lung tumors.
We have demonstrated the presence of CYP2E1 protein in a catalytically active form in lung tumors, differences being observed between the tumors and normal tissues from the same patients. Indeed, a higher microsomal CYP2E1 N-nitrosodimethylamine (NDMA) demethylase activity was present in normal tissues compared to tumors and was accompanied by corresponding change in CYP2E1 protein concentration, as shown by Western blot analysis. The catalytic activity among tumors differed from that among normal tissues with statistical significance of p < 0.01. CYP2E1 mRNA was present in lung tumors and less expressed compared to normal tissues from the same individuals. In order to understand the regulation of CYP2E1 gene expression, we studied the methylation status of the CYP2E1 gene in human lung tumors and normal tissues from the same patients and observed that a hypomethylation was associated with a hypoexpression of the CYP2E1 gene in lung tumors.
Botto
F
F
EA878: Laboratoire de biologie moléculaire appliquée au médicament, Marseille, France.
Seree
E
E
el Khyari
S
S
Cau
P
P
Henric
A
A
De Meo
M
M
Bergeron
P
P
Barra
Y
Y
D001483:Base Sequence; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000096:biosynthesis*; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008745:Methylation; D008861:Microsomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012907:Smoking
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating