title: Expression of CYP3A4 in human breast tumour and non-tumour tissues.
abstract: Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays a major role in the activation of procarcinogens such as polycyclic hydrocarbon dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs including tamoxifen which is used in breast cancer therapy. Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP3A4 protein is expressed in both tumour and normal breast tissue with an increased expression in tumours.
authors.affiliation: Department of Pathology, Demetevler Oncology Hospital, Ankara, Turkey.
authors.forename: Nilgün
authors.initials: N
authors.lastname: Kapucuoglu
authors.forename: Tulay
authors.initials: T
authors.lastname: Coban
authors.forename: Hannu
authors.initials: H
authors.lastname: Raunio
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Edwards
authors.forename: Alan R
authors.initials: AR
authors.lastname: Boobis
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Iscan
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008593:Menopause; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D012907:Smoking
chemical_list: D011960:Receptors, Estrogen; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human