Aromatase and regulating the estrogen:androgen ratio in the prostate gland

Ellem, Stuart John; Risbridger, Gail P.

doi:10.1016/j.jsbmb.2009.10.015

Cited by 137 publications

(139 citation statements)

References 80 publications

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“…However, the availability of highly accessible blood tests for prostate-specific antigen (PSA) has revolutionized the diagnosis of PC over the past 3 decades (2). Recent statistics demonstrate that PC is now the second leading cause of cancer death and the most commonly diagnosed malignancy in men in developed countries as a result of the increased availability of prostate-specific antigen testing (1,(3)(4)(5)(6).…”

Section: Epidemiologymentioning

confidence: 99%

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Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

Kachakova¹,

Mitkova²,

Popov³

et al. 2016

Turk J Med Sci

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Background/aim: The aim of our study was to elucidate the role of polymorphisms in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in Bulgarian patients. Materials and methods:We genotyped 246 PC patients and 261 controls (155 with benign prostate hyperplasia and 107 healthy population controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis. Results:The allele and genotype frequencies of most of the studied variants did not differ significantly between cases and controls. Increased frequencies of the C/C genotype and C allele of rs1056837 in CYP1B1, and genotype 7/8 of the (TTTA)n repeat polymorphism in CYP19, were observed in patients in comparison with controls.The 8/9 and the 7/12 genotypes of (TTTA)n in CYP19 showed suggestive evidence for association with decreased prostate cancer risk and the risk for aggressive disease, respectively. The haplotype analysis revealed 2 CYP1B1 haplotypes associated with PC risk reduction. Conclusion:Some CYP1B1 haplotypes and genotypes of the CYP19 (TTTA)n repeat appeared to be associated with disease risk or aggressiveness in Bulgarian PC patients. In contrast, the SRD5A2 polymorphisms (V89L and (TA)n repeat), the CAG repeat in AR, and the Arg264Cys variant in CYP19A1 are most likely not implicated in prostate carcinogenesis.

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Section: Epidemiologymentioning

confidence: 99%

“…Some authors believe that high estrogen and low testosterone lead to the development of inflammation upon aging and the emergence of premalignant lesions (1), but others have shown that administration of testosterone induces prostate tumors in laboratory animals and PC regress after antiandrogen therapy (11).…”

Section: Risk Factorsmentioning

confidence: 99%

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

Kachakova¹,

Mitkova²,

Popov³

et al. 2016

Turk J Med Sci

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“…One of them, aromatase, catalyzes the estrogen biosynthesis from androgens (22). The aberrant expression of aromatase has an important role in the development of prostate malignancy (23). Also, highly expressed enzyme 5α-reductase converts testosterone (T) into dihydrotestosterone (DHT).…”

Section: Steroidogenic Capacity and Erβmentioning

confidence: 99%

The Role of Estrogen Receptor β in Prostate Cancer

Christoforou

Christopoulos

Koutsilieris

2014

Mol Med

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Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the recent experimental findings of ERβ signaling in the prostate.

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“…These two receptors play significantly different roles within the prostate tissue, with ERα mediating the adverse effects upon stimulation, such as aberrant proliferation, inflammation and premalignant pathology. Conversely, the prevailing ER subtype within the prostate is ERβ, which appears to mediate the beneficial effects of oestrogen stimulation by acting in a putative protective role against carcinogenesis (Linja et al 2003, Risbridger et al 2007, Ellem & Risbridger 2010. Rogenhofer et al (2012) RP + TURP 233 IHC Slight correlation with progression Lotan et al (2000) 32 ISH Not prognostic RARβ Rogenhofer et al (2012) RP + TURP 233 IHC Not prognostic Lotan et al (2000) 32 ISH Lost in cancer RARγ Rogenhofer et al (2012) RP + TURP 233 IHC Not prognostic Lotan et al (2000) 32 ISH Not prognostic RXRα Rogenhofer et al (2012) RP Animal models have been used to elucidate the roles that oestrogen receptors and oestrogen may play in prostate carcinogenesis.…”

Section: Oestrogen Receptors (Erα or Nr3a1 And Erβ Or Nr3a2)mentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

Leach

Powell

Bevan

2016

Endocrine-Related Cancer

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Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease -hence the quest for new effective therapies for 'castrate-resistant' prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC, other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence, the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This review aims to provide a snapshot of the current knowledge of the roles of different nuclear receptors in prostate cancer -a rapidly evolving field of research.

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Aromatase and regulating the estrogen:androgen ratio in the prostate gland

Cited by 137 publications

References 80 publications

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

The Role of Estrogen Receptor β in Prostate Cancer

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

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