Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q16481 (Aromatase protein)
 6 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen production by the preimplantation equine embryo is presumed to be important in maternal-conceptus communication in the mare. The synthesis of C(18) estrogens from C(19) androgens requires cytochrome P450 aromatase (P450(arom)) in the conceptus, but little information is available on the specific tissue location or potential developmental patterns of expression for the horse. The goal of this research was to localize P450(arom) in the equine conceptus by immunocytochemistry and in situ hybridization. Intact blastocyst-stage embryos were collected by nonsurgical flush on Days 12-15 of pregnancy, fixed in 4% paraformaldehyde, and paraffin-embedded. Aromatase protein was localized using rabbit anti-human placental aromatase antiserum with a detection system utilizing peroxidase and 3-amino-9-ethylcarbazole. For in situ hybridization, tissue sections were incubated with sense or antisense [(35)S]UTP-labeled cRNA probes prepared from equine aromatase cDNA. Aromatase protein and transcript were abundant in the extraembryonic trophectoderm but absent from embryonic ectoderm. No P450(arom) expression was detected in abembryonic endoderm or mesoderm. Aromatase expression was demonstrated in the endoderm beneath the disc (hypoblast). This pattern of P450(arom) expression in the equine blastocyst closely resembles that seen transiently in the porcine embryo, suggesting that regulatory mechanisms conferring tissue specificity may be conserved.
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PMID:Tissue-specific localization of cytochrome P450 aromatase in the equine embryo by in situ hybridization and immunocytochemistry. 1077 60

Tissue-specific aromatase production is significant in breast cancer and osteoporosis. Prostatic aromatase expression has been equivocal, and any local actions of estrogens are considered secondary to centrally mediated androgen suppression. We examine local aromatase expression and estrogen biosynthesis in the human prostate. Pure samples of stroma and epithelia from biopsy tissues were isolated by laser capture microdissection. Aromatase protein was detected by Western blot analysis, mRNA by RT-PCR, and enzyme activity by tritiated water assay, whereas promoter use was examined by real-time PCR. In nonmalignant prostate tissues, aromatase mRNA expression was absent from epithelium, but did localize to stroma. Presence of protein was confirmed, and expression was driven by promoter PII. Aromatase was expressed and active in LNCaP, PC3, and DU145 cells in addition to microdissected epithelial tumor cells; benign prostate epithelial cells showed no expression or activity. Promoter use in LNCaP and microdissected tumor cells was via PII, whereas PC3 and DU145 cells used promoter I.4. This study demonstrates local estrogen biosynthesis in prostate-induced aromatase gene expression in malignancy and potential alteration of aromatase promoter use with disease progression. These data provide a basis for continued investigation of local estrogen production and its potential role in prostate disease.
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PMID:Local aromatase expression in human prostate is altered in malignancy. 1512 75

Breast cancer is a frequently reported cancer in women all over the world. Several methods available to cure the breast cancer based on stage. This study focused on chemoprevention drugs of Aromatase, a potential target in breast cancer. Natural variants of Aromatase are very common; they have been collected and modeled, optimized the energy of mutated Aromatase protein. Reversible (Anastrozole) and irreversible (Exemestane) Aromatase inhibitors are selected and performed molecular docking studies of each drug against each variant to see the binding affinity impact on protein variant and drugs. In this comparative study, Anastrozole, a cumene derivative showed more binding affinity and Diethylstilbestrol showed weak binding affinity against among all drugs. The comparative molecular docking revealed that the binding affinity between drug and Aromatase protein variant is imprecise but fairly close; therefore the protein variants of Aromatase can be conceived to be equal for chemoprevention of breast cancer therapy.
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PMID:Impact of Aromatase protein variants and drug interactions in breast cancer: a molecular docking approach. 2271 91

Aromatase protein is overexpressed in the breasts of women affected with cancer. In the endoplasmic reticulum (ER), signal sequence and signal anchors (SAs) facilitate translocation and topology of proteins. To understand the function of type-I SAs (SA-Is), we evaluated translocation of aromatase, whose signal anchor follows a hydrophilic region. Aromatase SA-I mediates translocation of a short N-terminal hydrophillic domain to ER lumen and integrates the protein in the membrane, with the remainder of the protein residing in the cytosol. We showed that lack of a signal peptidase cleavage site is not responsible for the stop-transfer function of SA-I. However, SA-I could not block the translocation of a full-length microsomal secretory protein and was cleaved as part of the signal sequence. We propose that interaction between the translocon and the region after the signal anchor plays a critical role in directing the topology of the protein by SA-Is. The positive charges in the signal sequence helped it to override the function of signal anchor. Thus, when signal sequence follows SA-I immediately, the interaction with the translocon is perturbed and topology of the protein in ER is altered. If signal sequence is placed far enough from SA-I, then it does not affect membrane integration of SA-I. In summary, we conclude that it is not just the SA-I, but also the region following it, which together affect function of aromatase SA-I in ER.
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PMID:Passenger protein determines translocation versus retention in the endoplasmic reticulum for aromatase expression. 2428 11

The biological roles of estrogen receptor 1 (ERS1), estrogen receptor 2 (ERS2), and aromatase (CYP19A1) genes in the development of non-small cell lung cancer (NSCLC) is unclear, as is the use of their expression as a prognostic factor. The aim of this study was to investigate the prognostic value of estrogen receptors and aromatase mRNA expression, along with aromatase protein concentration, in resected NSCLC patients. Tumor and non-tumor lung tissue samples were analyzed for the mRNA expression of ERS1, ERS2 and CYP19A1 by RT-PCR. Aromatase concentration was measured with an ELISA. A total of 96 patients were included. ERS1 expression was significantly higher in non-tumor tissue than in tumor samples. Two gene expression categories were created for each gene (and protein): high and low. ERS1 high category showed increased overall survival (OS) when compared to the low expression category. Aromatase protein concentration was significantly higher in tumor samples. Higher ERS1 expression in tumor tissues was related to longer overall survival. The analysis of gene expression combinations provides evidence for longer OS when both ERS1 and ERS2 are highly expressed. ESR1, alone or in combination with ERS2 or CYP19A1, is the most determining prognostic factor within the analyzed 3 genes. It seems that ERS1 can play a role in NSCLC prognosis, alone or in combination with other genes such as ERS2 or Cyp19a1. ERS2 in combination with aromatase concentration could have a similar function.
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PMID:Estrogen receptor 1 gene expression and its combination with estrogen receptor 2 or aromatase expression predicts survival in non-small cell lung cancer. 2531 Feb 21