Cytochrome p450 and glutathione transferase expression in human breast cancer.
OBJECTIVE
The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems may influence the biological effects of carcinogens, including estrogens. As such, these enzymes may predict the developmental risk of breast cancer, as well as be potential targets for chemoprevention. The purpose of this study was to compare the expression of GST-Pi and CYPs 1A1, 2B6, 2E1, and 3A4 in paired samples of normal and malignant breast tissue from patients with breast cancer and women undergoing reduction mammoplasty.


METHODS
Expression of CYPs 1A1, 2B6, 2E1, 3A4, and GST-Pi was quantified in breast tissue from 33 patients with breast cancer and in 17 women without history of cancer who underwent reduction mammoplasty. The expression of CYP 1A1, 2B6, 2E1, 3A4, and GST-Pi was quantified by immunoblotting.


RESULTS
CYP 1A1, 2E1, and 3A4 expression was significantly lower (P < 0.05) in malignant tissue as compared with morphologically normal adjacent tissue. Conversely, GST-Pi expression was marginally lower in the normal tissue (P = 0.08). No significant difference in enzyme expression was seen between the tissue from reduction mammoplasty and normal tissue from breast cancer patients. There was a trend for higher expression of CYP 2B6 and GST-Pi in the estrogen receptor expressing tumors than those tumors without expression (P > 0.28).


CONCLUSIONS
The expression of these enzymes was similar in morphologically normal breast tissue from patients with or without breast cancer. The expression of CYPs was down-regulated in the tumor tissue. The clinical significance of CYP alterations in breast cancer will need further characterization.
El-Rayes
Basil F
BF
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Ali
Shadan
S
Heilbrun
Lance K
LK
Lababidi
Samir
S
Bouwman
David
D
Visscher
David
D
Philip
Philip A
PA
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065702:Cytochrome P-450 CYP2B6; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D016462:Mammaplasty; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
D007527:Isoenzymes; D011960:Receptors, Estrogen; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C104464:CYP3A protein, human; D019363:Cytochrome P-450 CYP1A1; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase