Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells

Otsuka, Takashi; Iguchi, Kazuhiro; Fukami, Kazuhiro; Ishii, Kenichiro; Usui, Shigeyuki; Sugimura, Yoshiki; Hirano, Kazuyuki

doi:10.1007/s13277-011-0209-y

Cited by 16 publications

(10 citation statements)

References 16 publications

(24 reference statements)

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“…LNCaP cells have a point-mutated AR (T877A), which broadens the ligand specificity (8,9). Since PSA expression was found to be highly induced by betamethasone (an agonist against the glucocorticoid receptor), which has a steroid structure, this induction was considered to be mediated through transactivation of the mutated AR.…”

Section: Resultsmentioning

confidence: 99%

Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells

et al. 2014

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Prostate cancer occurs more frequently among older males and such elderly individuals often have chronic underlying disorders for which various drugs are administered for treatment. The levels of prostate-specific antigen (PSA), a widely used prostate cancer marker, are influenced by a number of drugs, such as non-steroidal anti-inflammatory drugs and statins. In the present study, the drugs prescribed to patients on a repeat prescription collected at the pharmacy of the Gifu Pharmaceutical University (Gifu, Japan) were examined for their effects on the levels of PSA expression in prostate cancer LNCaP cells. Among the 14 drugs investigated, betamethasone, an agonist of the glucocorticoid receptor, was found to increase the levels of PSA mRNA expression in the LNCaP cells. This betamethasone-induced expression was mediated, at least in part, through androgen receptor (AR) transcriptional activation. Dexamethasone, a typical agonist of the glucocorticoid receptor, was also found to stimulate the AR transcriptional activity, however, to a lesser extent than betamethasone. Therefore, it would be interesting to examine in future studies whether the serum PSA levels in prostate cancer patients are influenced by betamethasone.

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Section: Resultsmentioning

confidence: 99%

Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells

et al. 2014

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“…Their overexpression and/or overactivation has been shown in a number of human cancers with various genomic, transcriptional, and posttranslational mechanisms, and are associated with refractory disease leading to poor outcomes [ 31 ]. In human prostate cancer, NCOAs have been reported to regulate cell proliferation and invasion and be involved in castration resistance, coupled with AR transcriptional activity [ 32 – 34 ]. NCOA2 has therefore been shown to play a role as a coactivator in the androgen-AR interaction [ 35 – 38 ]; however, there has been no study examining the function of NCOAs in prostate cancer cells treated with antiandrogens.…”

Section: Discussionmentioning

confidence: 99%

Corepressive function of nuclear receptor coactivator 2 in androgen receptor of prostate cancer cells treated with antiandrogen

et al. 2016

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BackgroundRecruitment of cofactors in the interaction of the androgen receptor (AR) and AR ligands plays a critical role in determining androgenic/antiandrogenic effects of the AR ligand on signaling, but the functions of key cofactors, including nuclear receptor coactivator (NCOA), remain poorly understood in prostate cancer cells treated with AR ligands.MethodsWe examined prostate cancer cell lines LNCaP and VCaP expressing mutated and wild-type ARs, respectively, to clarify the significance of NCOAs in the effect of antiandrogens. Hydroxyflutamide showed antagonistic activity against VCaP and an agonistic effect on LNCaP. Bicalutamide served as an antagonist for both. We analyzed mRNA transcription and protein expression of NCOAs in these cells pretreated with dihydrotestosterone and thereafter treated with the mentioned antiandrogens. Transcriptional silencing of candidate NCOAs and AR was performed using small interfering RNA (siRNA). Cell proliferation was evaluated with MTT assay.ResultsLNCaP treated with bicalutamide showed an about four-fold increase in the expression of NCOA2 mRNA compared to those pretreated with dihydrotestosterone alone (P <0.01). In VCaP pretreated with dihydrotestosterone, transcriptions of NCOA2 and NCOA7 were slightly increased with bicalutamide (1.96- and 2.42-fold, respectively) and hydroxyflutamide (1.33-fold in both). With Western blotting, the expression of NCOA2 protein also increased in LNCaP cells treated with bicalutamide compared with that in control cells pretreated with dihydrotestosterone alone. Following silencing with siRNA for NCOA2, PSA levels in media with LNCaP receiving bicalutamide were elevated compared with those in non-silencing controls (101.6 ± 4.2 vs. 87.8 ± 1.4 ng/mL, respectively, P =0.0495). In LNCaP cells treated with dihydrotestosterone and bicalutamide, NCOA2-silencing was associated with a higher proliferation activity compared with non-silencing control and AR-silencing.ConclusionNCOA2, which has been thought to be recruited as a coactivator, possibly plays a corepressive role in AR of prostate cancer cells when treated with antiandrogens, suggesting its potential as a therapeutic target.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2378-y) contains supplementary material, which is available to authorized users.

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“…Cell lysis and Western blotting were performed as described previously (Otsuka et al, 2011). Cells were lysed in RIPA buffer (10 mM Tris‐HCl [pH 7.5], 1% Nonidet P‐40, 0.1% sodium deoxycholate, 0.1% sodium dodecyl sulfate [SDS], 150 mM NaCl, and 1 mM EDTA) containing 200 μM phenylmethylsulfonyl fluoride, 5 μg/mL aprotinin, 1 μg/mL leupeptin, 1 μg/mL pepstatin, 2 mM sodium orthovanadate, 10 mM sodium fluoride, and 2.5 mM β‐glycerophosphate.…”

Section: Methodsmentioning

confidence: 99%

Antiandrogenic Activity of Resveratrol Analogs in Prostate Cancer LNCaP Cells

Iguchi

Toyama

Ito

et al. 2012

Journal of Andrology

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The suppression of androgen signaling is a therapeutic target for the treatment of prostate cancer. Resveratrol (3,49,5-trihydroxystilbene) is known to inhibit the function of the androgen receptor (AR). In the present study, we investigated the antiandrogenic activities of resveratrol analogs in order to identify a potent antiandrogen compound. Resveratrol analogs were isolated from plants or were semisynthesized from resveratrol. AR transcriptional activity was measured in prostate cancer LNCaP cells using a luciferase assay with the MMTV-luc reporter plasmid. Among the resveratrol analogs tested, 49-O-methylresveratrol (3,5-dihydroxy-49-methoxystilbene) was the most effective inhibitor of AR transcriptional activity. Introduction of a methoxy group to the C-49 of resveratrol and its analogs increased their antiandrogenic activity compared with the unmodified counterparts. Conversely, modification of the 3-and/or 5-hydroxyl groups reduced the antiandrogenic activity. 49-O-methylresveratrol was more effective than resveratrol in inhibiting Akt phosphorylation, which is related to AR signaling, in LNCaP cells. The hydroxyl groups in resveratrol play a key role in their antiandrogenic effect by modulating AR transcriptional activity.

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Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells

Cited by 16 publications

References 16 publications

Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells

Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells

Corepressive function of nuclear receptor coactivator 2 in androgen receptor of prostate cancer cells treated with antiandrogen

Antiandrogenic Activity of Resveratrol Analogs in Prostate Cancer LNCaP Cells

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