Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells.

Corbin, C. J.; Graham-Lorence, Sandra E.; McPhaul, Michael J.; Mason, J. Ian; Mendelson, Carole R.; Simpson, Evan R.

doi:10.1073/pnas.85.23.8948

Cited by 262 publications

(115 citation statements)

References 30 publications

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“…cDNA ClOneS having 4 kbp inserts recently isolated by McPhaul et al [ 121 and by Corbin et al [13]. These findings suggest that the expression of human placental P-45OARoM is more complicated than previously anticipated.…”

Section: P-450arommentioning

confidence: 81%

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Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P‐450

Toda¹,

M²,

Mitsuuchi³

et al. 1989

FEBS Letters

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Two cDNA clones for human placental aromatase P-450 (P-450 AROM) have been isolated and sequenced. The insert of one clone (2894 bp) contains an open reading frame encoding a protein consisting of 503 amino acid residues together with a 49 bp S-untranslated stretch and a 1336 bp 3'-noncoding region to which a poly(A) tract is attached. Three potential poly(A) addition signals are detected in this 3'noncoding region. The other clone contains a shorter cDNA insert, the nucleotide sequence of which overlaps with most of the sequence of the longer cDNA insert (nucleotides 36-2355) except for one nucleotide substitution. The 3'noncoding region of this shorter cDNA is only 846 bp in length, but a poly(A) tract is also attached to its 3'-terminus. Northern blot analysis of human placental RNA reveals the presence of two major mRNA species of 3.4 and 2.9 kb when probes excised from the overlapping region of these two cDNAs are employed. The 2.9 kb mRNA is not detected, however, when a fragment of the non-overlapping region of the longer cDNA is used as a probe. It is therefore concluded that the two major species of P-4SOAROM mRNA are formed as a consequence of alternative processing of precursor mRNA(s).

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Section: P-450arommentioning

confidence: 81%

“…More recently, full-length cDNAs for P-45OAROM have been isolated from chicken ovarial [12] and human placental [13,14] cDNA libraries and sequenced.…”

Section: P-450arommentioning

confidence: 99%

Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P‐450

Toda¹,

M²,

Mitsuuchi³

et al. 1989

FEBS Letters

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show abstract

“…The target chosen was at bases 826 845 of the P450arom gene coding sequence [19], where there is a 20 bp purine-rich sequence interrupted by three CG pairs (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…The selected 20bp sequence present within exon VII [19] included three CG pairs, and so did not represent a perfect triplex target. Using a modification of the established rules [3], it was possible to design a third strand ODN which demonstrated effects in electrophoretic mobility shift assays compatible with triplex formation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of aromatase expression by a psoralen‐linked triplex‐forming oligonucleotide targeted to a coding sequence

et al. 1995

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The cytochrome P450 enzyme aromatase (P450arom) is an important target in breast cancer treatment. We have designed a 20-base pyrimidine oligodeoxynucleotide (ODN) which forms a sequence-specific triple helix (triplex) with a purine-rich tract in the P450arom coding sequence. The psoralen-linked ODN (Pso20T) formed photo-induced cross-linked products with target double-stranded DNA. Cross-linked adducts formed in vitro between ODNs and P450arom expression constructs were used to transfect COS and human MCF-7 breast cancer cells. Levels of aromatase transcripts and enzyme activity were significantly lower in cultures transfected with Pso20T-treated cDNA relative to controls. Pso20T had a lesser inhibitory effect on aromatase expression from a mutant P450arom construct, consistent with predicted effects of the mutations on triplex formation. These results are compatible with triplex-mediated interruption of transcription within intact cells.

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“…Adipose tissue is the primary site of aromatization, but aromatase can be found at other sites such as the brain (hypothalamus, limbic system, and cerebral cortex), breast, placenta, liver, muscle, bone (osteoblast and chondrocyte), testes (Leydig cell and germ cell), vasculature (smooth muscle cell), and skin (fibroblast and hair follicle) (4,5). Peripherally synthesized estrogen seems to have predominantly local effects (2,3,6).…”

Section: Introductionmentioning

confidence: 99%

The use of aromatase inhibitors in boys with short stature: what to know before prescribing?

Linardi¹,

Damiani

Longui

2017

Arch. Endocrinol. Metab.

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Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.

show abstract

Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells.

Cited by 262 publications

References 30 publications

Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P‐450

Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P‐450

Inhibition of aromatase expression by a psoralen‐linked triplex‐forming oligonucleotide targeted to a coding sequence

The use of aromatase inhibitors in boys with short stature: what to know before prescribing?

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