Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

Čulig, Zoran; Hobisch, Alfred; Hittmair, A; Cronauer, Marcus V.; Radmayr, Christian; Zhang, Ju; Bartsch, Georg; Klocker, Helmut

doi:10.1002/(sici)1097-0045(19970701)32:2<106::aid-pros5>3.0.co;2-k

Cited by 65 publications

(24 citation statements)

References 39 publications

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“…However, steroid hormone receptors can be activated in the absence of hormone by phosphorylation. In the case of the AR, this possibility was demonstrated by Culig et al 9 In cells of the prostate tumour line DU-145 transfected with an AR expression vector (these cells are normally receptor-negative), the receptor can be activated by IGF-I as effectively as by the powerful synthetic androgen R-1881. Keratinocyte growth factor (a member of the fibroblast growth factor (FGF) family) and epidermal growth factor were also activated in some conditions.…”

Section: Protein Alterationssupporting

confidence: 64%

“…43,46,47 Other mutations can make the AR capable of activation by adrenal androgens (dehydroepiandosterone and androstenedione). 9,48,49 Another paradoxical situation is when advanced prostate adenocarcinomas resistant to hormone treatment react to androgen therapy. 50 These tumours have acquired a new phenotype following chronic androgen privation.…”

Section: Hormone-refractory Prostate Cancermentioning

confidence: 99%

See 1 more Smart Citation

Hormone-refractory prostate cancer: a multi-step and multi-event process

Taille

Vacherot²,

Salomon³

et al. 2001

Prostate Cancer Prostatic Dis

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Since the pioneering studies of Huggins in 1941, it has been known that prostate cancer cells, like certain normal epithelial cells, can chronically depend on a critical level of androgenic stimulation for their continuous growth and survival. The entire issue of the development of resistance to androgen ablation therapy for metastatic prostate cancer is based on the fact that a portion of cells can survive without androgen stimulation. The cell mechanism of androgen independent status is unclear. For some authors, a portion of the cells present within a patient with a prostate cancer before therapy is naturally androgen independent (selection hypothesis). However, this hypothesis does not consider gene alteration during prostate cancer natural history and probably hormone-refractory prostate cancer (HRPC) is due to a multi-step and multi-event process. In this literature review, different cell pathways that lead to HRPC are described.

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Section: Protein Alterationssupporting

confidence: 64%

Section: Hormone-refractory Prostate Cancermentioning

confidence: 99%

Hormone-refractory prostate cancer: a multi-step and multi-event process

Taille

Vacherot²,

Salomon³

et al. 2001

Prostate Cancer Prostatic Dis

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“…Synergistic or additive increases in the transcription of AREdriven reporters have been reported in the presence of androgen and compounds that activate protein kinase pathways (34,(61)(62)(63)(64). We observed a synergistic induction of the ARE-driven reporters in response to a saturating concentration of R1881 and IL-6, which may suggest that an additional mechanism to that used solely by R1881 is involved in the IL-6 pathway.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Androgen Receptor N-terminal Domain by Interleukin-6 via MAPK and STAT3 Signal Transduction Pathways

Ueda

Bruchovsky

Sadar

2002

Journal of Biological Chemistry

348

336

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“…Recent studies have shown that growth factors, peptide hormones and substances which directly activate protein kinases participate in AR signalling. Ligand-independent activation of the AR by growth factors and protein kinase A activators and synergistic effects of these activators and androgen were reported (Culig et al, 1994(Culig et al, , 1997aNazareth and Weigel, 1996). Furthermore, androgen-like effects of epidermal growth factor and keratinocyte growth factor during sexual development and AR-dependent stimulation of PSA secretion in explants of prostate tissue by a cyclic adenosine monophosphate analogue were described (Gupta et al, 1996;Nakhla et al, 1997;Thomson et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

Hoffmann²,

et al. 1999

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Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 n M of the synthetic androgen methyltrienolone (R1881), whereas 0.01 n M of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 n M , whereas 0.1 n M of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the non-steroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention. © 1999 Cancer Research Campaign

show abstract

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

Cited by 65 publications

References 39 publications

Hormone-refractory prostate cancer: a multi-step and multi-event process

Hormone-refractory prostate cancer: a multi-step and multi-event process

Activation of the Androgen Receptor N-terminal Domain by Interleukin-6 via MAPK and STAT3 Signal Transduction Pathways

Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system

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