[An immunohistochemical study of aromatase, estrogen 4-hydroxylase and fatty acid synthetase in breast cancer tissues from BRCA1 mutation carriers].
Breast cancer in germline BRCA1 mutation carriers features a peculiar endocrine and metabolic profile which is yet to be studied properly in clinical settings. We used a novel immunohistochemical method to compare expression levels of aromatase, estrogen 4-hydroxylase (CYP1B1) and fatty acid synthetase in breast cancer tissues from 12 BRCA1 mutation carriers and 22 non-carriers. Rates of aromatase in carriers were significantly higher than in control (p=0.04) to match the data obtained earlier in cell lines employed in down-regulation of the wild BRCA1 gene. These findings make a case for use of aromatase inhibitors in such patients. No differences in CYP1B1 and fatty acid synthetase expression levels were found between the mutation and the wild BRCA1 gene groups. Further search is warranted for manifestations of excess genotoxic effects of estrogens and enhanced lipogenesis in BRCA1 mutation carriers.
L M
LM
Bershteĭn
K M
KM
Pozharisskiĭ
N A
NA
Maksimova
A Iu
AIu
Kovalevskiĭ
E N
EN
Imianitov
D000328:Adult; D001141:Aromatase / Q000032:analysis*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D015536:Down-Regulation; D054890:Fatty Acid Synthase, Type I / Q000032:analysis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation
D047072:Aromatase Inhibitors; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I