Disease relevance of BRN 1999480

• In many in situ carcinomas, however, 4-hydroxyestrone immunostaining was not only preserved but even more intense than in normal mammary epithelium [1].
• Finally, the endogenous catechol estrogen metabolite 4-hydroxyestrone (4-OHE) was considerably less effective at inducing DNA damage and apoptosis in breast cancer cell lines than 4-OHEN [2].

High impact information on BRN 1999480

• Using reverse transcriptase-polymerase chain reaction, immunocytochemistry, immunoblot analyses, and assays of glucuronidation of 4-hydroxyestrone, we show that UGT2B7 is expressed in human mammary epithelium, and that its expression is dramatically reduced in invasive breast cancers [1].
• However, the basal level of p53 was higher in resistant clones and addition of 2- or 4-hydroxyestrone increased p53 to levels equivalent to those observed following UVB irradiation [3].
• In contrast, 2- and 4-hydroxyestrone did not increase the level of pS2 mRNA [3].
• Conversion of estrone to 2- and 4-hydroxyestrone by hamster kidney and liver microsomes: implications for the mechanism of estrogen-induced carcinogenesis [4].
• These novel data are significant because patients with fibrocystic disease are at slightly elevated risk for developing breast cancer and 16alpha-hydroxyestrone and 4- hydroxyestrone are reported carcinogens [5].

Biological context of BRN 1999480

• Although all estrogens significantly reduced lipid peroxidation, 4-hydroxyestrone was far more potent than either equilin or 17alpha-dihydroequilin in inhibiting TBARS formation in lipoproteins induced by Cu2+ [6].

Anatomical context of BRN 1999480

• Following expression of UGT171 in COS-1 cells, glucuronidation activity was identified for small phenolic molecules like 4-nitrophenyl, bulky phenols as represented by 4-hydroxybiphenol and octylgallate, as well as 4-hydroxyestrone [7].
• In contrast, kidney microsomes derived from castrated male hamsters metabolized E1 to mainly 17 beta-estradiol, 2- and 4-hydroxyestrone, 6 alpha-hydroxyestrone, 6 beta-hydroxyestrone and one monohydroxyestradiol metabolite [8].

Associations of BRN 1999480 with other chemical compounds

• Expression of UGT2B7, a UDP-glucuronosyltransferase implicated in the metabolism of 4-hydroxyestrone and all-trans retinoic acid, in normal human breast parenchyma and in invasive and in situ breast cancers [1].
• In vitro metabolic conjugation of the catechol estrogens, 2-hydroxyestrone and 4-hydroxyestrone, has been investigated by means of HPLC with electrochemical detection [9].

Analytical, diagnostic and therapeutic context of BRN 1999480

• Radioimmunoassay for 4-hydroxyestrone 4-methyl ether in human urine [10].
• In vitro O-methylation of 4-hydroxyestrone monosulfates has been examined by means of high-performance liquid chromatography with electrochemical detection [11].

References