Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1.
A novel human cytochrome P450, CYP2W1, was cloned and expressed heterologously. No or very low CYP2W1 mRNA levels were detected in fetal and adult human tissues, expression was however seen in 54% of human tumor samples investigated (n=37), in particular colon and adrenal tumors. Western blotting also revealed high expression of CYP2W1 in some human colon tumors. In rat tissues, CYP2W1 mRNA was expressed preferentially in fetal but also in adult colon. The CYP2W1 gene was shown to encompass one functional CpG island in the exon 1-intron 1 region which was methylated in cell lines lacking CYP2W1 expression, but unmethylated in cells expressing CYP2W1. Re-expression of CYP2W1 was seen following demethylation by 5-Aza-2'-deoxycytidine. Transfection of HEK293 cells with CYP2W1 caused the formation of a properly folded enzyme, which was catalytically active with arachidonic acid as a substrate. It is concluded that CYP2W1 represents a tumor-specific P450 isoform with potential importance as a drug target in cancer therapy.
Karlgren
Maria
M
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
Gomez
Alvin
A
Stark
Katarina
K
Svärd
Jenny
J
Rodriguez-Antona
Cristina
C
Oliw
Ernst
E
Bernal
Maria Luisa
ML
Ramón y Cajal
Santiago
S
Johansson
Inger
I
Ingelman-Sundberg
Magnus
M
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000378:metabolism; D015153:Blotting, Western; D002384:Catalysis; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003106:Colon / Q000196:embryology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism; D018899:CpG Islands; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D019175:DNA Methylation; D000077209:Decitabine; D005091:Exons; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D017510:Protein Folding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection
D020033:Protein Isoforms; D012333:RNA, Messenger; D016718:Arachidonic Acid; D000077209:Decitabine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2; D001374:Azacitidine