Immunohistochemical study of cytochrome P450 2C and 3A in human non-neoplastic and neoplastic tissues.
Organ and cellular distribution and expression constancy of microsomal cytochrome P450 (CYP) 2C and 3A in humans were studied with new polyclonal antibodies to CYP2C (MP-1) and 3A (NF-2) active in formalin-fixed, paraffin-embedded tissues. Antibodies were raised against purified human CYP2C9 and CYP3A4. On western blotting, MP-1 reacted with 2C8, 2C9, 2C18 and 2C19, and NF-2 with 3A4. In both frozen and paraffin sections, hepatocytes showed diffuse immunoreactivity with MP-1 and centrilobular staining with NF-2. In-paraffin sections of 40 kinds of nonneoplastic tissues, epithelium of the small and large intestine, bile duct, nasal mucosa, kidney and adrenal cortex stained positively with both MP-1 and NF-2 antibodies. Epithelium of gastric fundic glands, salivary glands, tracheobronchial glands, Brunner's glands, the prostate, uterine cervix and nasopharynx showed definite reactivity with MP-1. Epithelium of the gastric mucosa with intestinal metaplasia, duodenum, gallbladder and intercalated ducts of the pancreas and chief cells of the parathyroid and the corpus luteum of the ovary reacted with NF-2. Among the neoplastic tissues, MP-1 reacted with pleomorphic adenoma of the salivary gland and carcinomas of six different organs, and NF-2 with those of 7 different organs. These results indicate that CYP2C and CYP3A are distributed widely and organ specifically, as well as being variably expressed in neoplastic and normal states.
Yokose
T
T
Pathology Division, National Cancer Center Research Institute East, Kashiwa, Chiba, Japan. tyokose@east.ncc.go.jp
Doy
M
M
Taniguchi
T
T
Shimada
T
T
Kakiki
M
M
Horie
T
T
Matsuzaki
Y
Y
Mukai
K
K
D000911:Antibodies, Monoclonal / Q000032:analysis; D000937:Antigen-Antibody Reactions; D001189:Aryl Hydrocarbon Hydroxylases; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000276:immunology; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D008862:Microsomes, Liver / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D009928:Organ Specificity; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis* / Q000276:immunology; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase; D010089:Oxidoreductases, N-Demethylating