Bicalutamide Demonstrates Biologic Effectiveness in Prostate Cancer Cell Lines and Tumor Primary Cultures Irrespective of Her2/neu Expression Levels

Gravina, Giovanni Luca; Festuccia, Claudio; Millimaggi, Danilo; Tombolini, Vincenzo; Dolo, Vincenza; Vicentini, Carlo; Bologna, Mauro

doi:10.1016/j.urology.2009.01.018

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…Indeed, it was used in many studies aimed at inactivate AR [23,71,72]. Moreover, the use of Bicalutamide in the maternal system has some advantages: i) permits AR nuclear localization also in a neuronal population, ii) binds to the ligand-binding domain of the AR to inhibit its transcriptional activity [73], iii)is rapidly absorbed and it has a short plasma elimination half-life [74], iv)in our experiments, Bicalutamidewas injected intraperitoneally in the mother and no teratogenic effects were observed (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

et al. 2017

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The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE), and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.

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Section: Discussionmentioning

confidence: 99%

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

et al. 2017

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“…It is possible that blocking ERBB-2 signaling will hinder the progression of PCa to androgen independence, or that ERBB-2 blockade will restore androgen dependence, suggesting that co-administration of an ERBB-2 inhibitor with an anti-androgen (e.g. bicalutamide) might have clinical benefits (45). Our transfection studies are consistent with this hypothesis, with the combination of miR-331-3p and bicalutamide giving stronger repression of androgen-stimulated PSA promoter activity than either miR-331-3p or bicalutamide alone (Figs.…”

Section: Discussionmentioning

confidence: 99%

miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer

Epis

Giles

Barker

et al. 2009

Journal of Biological Chemistry

148

123

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MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently overexpressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells.

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“…The use of bicalutamide may be an alternative in these patients, as studies have shown that it may have a use in HER-2-positive patients. [17] Studies in vitro with cells lines have demonstrated the importance of specific anti-HER-2 agents trastuzumab[18] and pertuzumab. [19] However, clinical studies have failed to show such a benefit of monotherapy[20] possibly because of the cell mixture of (HER-2-positive and negative cells).…”

Section: Discussionmentioning

confidence: 99%

Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol

et al. 2011

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Introduction:HER-2 expression in prostate cancer is associated with a worse prognosis and is suggested to play a role in androgen resistance. We present a study of HER-2 expression in circulating tumor cells and micrometastasis in bone marrow and the effect of androgen blockage or DES in the presence of HER-2 expressing cells.Patients and Methods:A multicenter study of men with prostate cancer, treated with surgery, radiotherapy, or observation, and with or without hormone therapy. Mononuclear cells were separated from blood and bone marrow aspirate by differential centrifugation, touch preps were made from bone marrow biopsy samples. Prostate cells were detected using anti-PSA monoclonal antibody and standard immunocytochemistry. Positive samples were processed using Herceptest® to determine HER-2 expression. After 1 year, patients were re-evaluated and the findings of HER-2 expression and PSA change compared with treatment.Results:Total 199 men participated, and 97 had a second evaluation 1 year later, frequency of HER-2 expression in circulating tumor cells and micrometastasis was 18% and 21%, respectively. There was no significant difference in HER-2 expression in the pretreatment group, after radical surgery or radiotherapy or with biochemical failure. Men with androgen blockade had a significantly higher expression of HER-2 (58%) (P =0.001). Of the 97 men with a second evaluation, 56 were in the observation arm, 27 androgen blockade, and 14 DES. Use of androgen blockade or DES significantly reduced serum PSA levels in comparison with observation (P =0.001). However, there was a significant increase in HER-2 expression in patients with androgen blockade (P =0.05) en comparison with observation or DES treatment. No patient with observation or DES became HER-2 positive, en comparison 4/22 patients initially HER-2 negative became HER-2 positive with androgen blockade.Conclusions:The results suggest that HER-2 positive cells are resistant to androgen blockade. In an environment lacking androgens, HER-2 positive cells are selected and survive, while HER-2 negative cells are eliminated thus decreasing the serum PSA. The population of HER-2 positive cells proliferate producing androgen-independent disease. DES does not increase HER-2 expression possibly by stimulating beta-estrogen receptors and blocking HER-2 androgen receptor activation.

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Bicalutamide Demonstrates Biologic Effectiveness in Prostate Cancer Cell Lines and Tumor Primary Cultures Irrespective of Her2/neu Expression Levels

Cited by 4 publications

References 18 publications

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer

Positive HER-2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol

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