It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed th...

PATIENT Female, 56 FINAL DIAGNOSIS: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: - Specialty: Oncology. OBJECTIVE Unusual clinical course. BACKGROUND The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reporte...

Aromatase [cytochrome P450 19 (CYP19)] is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors are of increasing importance in the treatment of breast cancer. We set out to identify and characterize genetic polymorphisms in the aromatase gene, CYP19, as a step toward pharmacogenomic studies of aromatase inhibitors. Specifically, we "resequenced" all coding exons, all upstream u...

Numerous steroid hormones, including 17β-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate...

Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine therapy for postmenopausal women with ER(+) breast cancers. Despite providing substantial improvements in patient outcome, aromatase inhibitor resistance remains a major clinical...

Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and adipose tissue. Aromatase enzyme is encoded by a single gene CYP 19A1 and its expression is controlled by tissue-specific promoters. Aromatase mRNA is primarily transcribed from promoter ...

The presence of aromatase activity, estrogen receptors, and estrogenic responsiveness in MCF-7 human breast cancer cells has allowed this cell line to be used as a unique in vitro system for investigating the biological activities of potentially therapeutic aromatase inhibitors. We now report the results of studies which have examined the cytotoxicity, antiaromatase, and intrinsic estrogenic ac...

7or-(4'-Amino)phenylthio-l,4-androstadiene-3,17-dione(7a-APTADD), a potent enzyme-activated irreversible inhibitor, was examined in two different human cell culture lines, MCF-7 human mammary carcinoma cells and JAr choriocarcinoma cells. Both the MCF-7 and JAr cell culture systems exhibit aromatase activity, and 7a-APTADD was evaluated for its aromatase-inhibitory activity, for its ability to ...

CYP1B1 and CYP19 (aromatase) have been shown to be expressed in breast tumors. Both enzymes are efficient estrogen hydroxylases, indicating the potential for overlapping substrate and inhibitor specificity. We measured the inhibition properties of aromatase inhibitors (AIs) against CYP1B1-catalyzed hydroxylation of 17beta-estradiol (E2) to determine whether CYP1B1 affects the disposition of AIs...