Aromatase, aromatase inhibitors, and breast cancer

Chumsri, Saranya; Howes, Timothy; Bao, Ting; Sabnis, Gauri; Brodie, Angela

doi:10.1016/j.jsbmb.2011.02.001

Cited by 313 publications

(230 citation statements)

References 104 publications

(123 reference statements)

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“…This suggests that in addition to steroidogenesis, Cyp17 may have a role in sperm structure and function (Liu et al 2005). Cyp19 (P450 aromatase) has also been found in a wide variety of tissues in addition to gonads: placenta, bone, adipose tissue, blood vessels, skin, endometrium and brain (see review in Chumsri et al (2011)). In the different mammalian species studied so far, P450 aromatase expression has been detected in several testicular somatic cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…In the different mammalian species studied so far, P450 aromatase expression has been detected in several testicular somatic cells (e.g. Leydig cells) as well as in gonocytes, spermatogonia, spermatocytes (preleptotene/-pachytene), spermatids and spermatozoa (see review in Chumsri et al (2011)). However, there is little information available in fish with respect to the question whether other testicular cell types express these enzymes as well.…”

Section: Introductionmentioning

confidence: 99%

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Cyp17a1 and Cyp19a1 in the zebrafish testis are differentially affected by oestradiol

Hinfray¹,

Nóbrega²,

Caulier³

et al. 2013

Journal of Endocrinology

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International audienceOestrogens can affect expression of genes encoding steroidogenic enzymes in fish gonads. However, little information is available on their effects at the protein level. In this context, we first analysed the expression of key steroidogenic enzyme genes and proteins in zebrafish testis, paying attention also to other cell types than Leydig cells. Gene expression was analysed by quantitative PCR on fluorescence-activated cell-sorting fractions coupled or not to differential plating, while protein synthesis was studied by immunohistochemistry using specific antibodies against zebrafish Cyp17a1, Cyp19a1a and Cyp19a1b. Furthermore, we have evaluated the effect of oestrogen treatment (17 beta-oestradiol (E-2), 10 nM) on the localization of these enzymes after 7 and 14 days of in vivo exposure in order to study how oestrogen-mediated modulation of their expression is linked to oestrogen effects on spermatogenesis. The major outcomes of this study are that Leydig cells express Cyp17a1 and Cyp19a1a, while testicular germ cells express Cyp17a1 and both, Cyp19a1a and Cyp19a1b. As regards Cyp17a1, both protein and mRNA seem to be quantitatively dominating in Leydig cells. Moreover, E-2 exposure specifically affects only Leydig cell Cyp17a1 synthesis, preceding the disruption of spermatogenesis. The oestrogen-induced suppression of the androgen production capacity in Leydig cells is a major event in altering spermatogenesis, while germ cell steroidogenesis may have to be fuelled by precursors from Leydig cells. Further studies are needed to elucidate the functionality of steroidogenic enzymes in germ cells and their potential role in testicular physiology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyp17a1 and Cyp19a1 in the zebrafish testis are differentially affected by oestradiol

Hinfray¹,

Nóbrega²,

Caulier³

et al. 2013

Journal of Endocrinology

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“…32 Several strategies have been investigated comparing the benefits of AIs and TAM in the adjuvant setting. 33 For initial treatment strategy for breast cancer, both anastrozole and letrozol have demonstrated a significant improvement in DFS after 5 years of study compared to the use of TAM alone or combined with anastrozole during the same time period. Nevertheless, a significant improvement in OS was not observed in these studies, probably due to crossover of a considerable number of patients after publication of the studies.…”

Section: Adjuvant Settingmentioning

confidence: 98%

Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review

Barros-Oliveira

Costa‐Silva

Andrade

et al. 2017

Rev. Assoc. Med. Bras.

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Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment. In metastatic disease, it is currently considered the first-line treatment for postmenopausal women with estrogen receptor-positive breast tumors. Anastrozole has shown promising results in the adjuvant treatment of early-stage breast cancer in postmenopausal women. It has also achieved interesting results in the chemoprevention of the disease. Therefore, due to the importance of anastrozole both for endocrine treatment and chemoprevention of hormone-sensitive breast cancer in postmenopausal women, we proposed the current literature review in the SciELO and PubMed database of articles published in the last 10 years.

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“…Normoxic expression of HIF-1α was reported to mediate HER2 effects on resistance to aromatase inhibitors in breast cancer cells [125]. Aromatase inhibitors reduce circulating levels of estrogen and are clinically used to treat breast cancer [126]. Resistance to these agents arises following a switch from dependence on estrogen receptor signaling to dependence on HER2 signaling [127].…”

Section: Erbb Family Receptorsmentioning

confidence: 99%