Expression and role of functional glucocorticoid receptors in the human androgen-independent prostate cancer cell line, DU145

Dondi, D.; Maggi, Roberto; Scaccianoce, Eugenia; Martini, L.; Motta, Marcella; Poletti, Angelo

doi:10.1677/jme.0.0260185

Cited by 23 publications

(25 citation statements)

References 23 publications

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“…The siRNAs of GR was previously shown to specifically abolish expression of GR (21) and RU486 was shown to inhibit the function of 15-LOX-2 (22,23). The luciferase assays showed that the treatment with siRNAs of GR was able to reverse the inhibitory effect of GR on promoter activities of LF4 and LF7, GR reduced luciferase activities of LF4 and LF7 to 60.73%±2.09 and 56.11±2.94, respectively, but these were up to 86.17±3.60 and 138.57±3.03, respectively after the treatment with siRNAs of GR.…”

Section: The Inhibitory Effect On 15-lox-2 Promoter Activity By Gr Wamentioning

confidence: 99%

Downregulation of 15-lipoxygenase 2 by glucocorticoid receptor in prostate cancer cells

Feng

Bai²,

Yang³

et al. 2010

Int J Oncol

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Abstract. 15-lipoxygenase 2 (15-LOX-2) is lost or significantly reduced in prostate cancer. However, the regulation of 15-LOX-2 remains unclear. In this study, we independently cloned the 5' upstream promoter fragments of 15-LOX-2 gene. Target DNA fragments each were cloned into an expression vector containing luciferase reporter gene, which were called LF1(-1533/+87), LF2(-628/+87), LF3(-253/+87), LF4(-157/ +87), LF5(-33/+87), LF6(-253/+1), and LF7(-157/+1). Each of these individual promoter fragments was transfected into primary prostate epithelial cells and prostate cancer LNCaP cells. The promoter activity gradually decreased with progressive deletions from LF2 to LF4. A significant drop was noted in the LF5. LF6 and LF7 that did not contain the 87-bp region downstream the transcription start site (TSS) have significant luciferase activities similar to those of corresponding fragments (LF3 and LF4) that contain 87-bp region downstream the TSS. This suggests that the 125-bp region (-157 to -33) of LF4 is critical for the promoter activity of 15-LOX-2 in the primary prostate epithelial cells PrEC and cancer cells LNCaP. Moreover, we discovered a specific glucocorticoid receptor (GR) responsive element (GRE) in this key region. The luciferase activities of the LF4 and LF7 were decreased in the LNCaP cells co-transfected with GR (hGR· or hGRß) expression vectors. This inhibitory effect is reversed after treatments with dexamethasone or two specific GR inhibitors (siRNAs of GR and RU486). Results from this study suggest a 125-bp region (-157 to -33) is critical for the 15-LOX-2 promoter activity in prostate epithelial cells and cancer cells, which was significantly downregulated by GR via the GRE in this region.

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Section: The Inhibitory Effect On 15-lox-2 Promoter Activity By Gr Wamentioning

confidence: 99%

Downregulation of 15-lipoxygenase 2 by glucocorticoid receptor in prostate cancer cells

Feng

Bai²,

Yang³

et al. 2010

Int J Oncol

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“…Thus, androgen ablation or blockade of AR function has been the cornerstone of treatment of advanced PC (1)(2)(3)(4). In contrast, we and others showed that signaling mediated by the glucocorticoid receptor (GR) plays a tumor suppressor role in prostate (5)(6)(7)(8)(9). PC cells expressing GR are sensitive to the growth-inhibitory effect of glucocorticoids in vitro and in vivo when grown as xenografts in athymic mice (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…One more mechanism of indirect negative gene regulation by GR involves inhibition of mitogenactivated protein kinases. This mechanism is used in different cells, including PC cells (5,7,13,15,16). Indirect, DNA-independent mechanisms of GR gene regulation seem to be critical for the antiinflammatory effects of glucocorticoids (13).…”

Section: Introductionmentioning

confidence: 99%

Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells

Yemelyanov¹,

Czwornog²,

Gera

et al. 2008

Cancer Research

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“…These results indicated that GR plays an important antiproliferative role in these macrophage cells. Although it is well known that GR mediates GC action by regulating the expression of target genes (Dondi et al 2001, Zhu et al 2004, Bladh et al 2005, but a few target genes have been known to mediate the antiproliferative effect of GC until now.…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoid (GC) is a significant hormone in regulating diverse physiological processes such as immune and inflammation responses, cell proliferation, differentiation, and apoptosis (Dondi et al 2001, Kudawara et al 2001, Distelhorst 2002, Yamamoto et al 2002. The common use of GC in treating inflammatory and autoimmune diseases is mostly due to its function of immunosuppression, for instance, inhibition of growth and induced apoptosis in lymphocytes, and repression of cytokine production in macrophages (Distelhorst 2002, Frankfurt & Rosen 2004.…”

Section: Introductionmentioning

confidence: 99%

Role of RHOB in the antiproliferative effect of glucocorticoid receptor on macrophage RAW264.7 cells

Wang

Chen²,

Wang³

et al. 2008

Journal of Endocrinology

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Although glucocorticoid (GC) has been reported to inhibit macrophage killing activity and cytokine production in response to proinflammatory stimuli, the effect of GC on macrophage proliferation is controversial. In our previous study, we found that inhibition of glucocorticoid receptor (GR) expression in murine macrophage cell line RAW264.7 cells (RAW-GR(K) cells) by RNAi significantly promoted cell proliferation. In the present study, we provide the evidence that the expression of Rhob, a member of Rho GTPases with anti-cancer character, remarkably decreased in RAW-GR(K) and RAW264.7 cells transiently transfected with GR-RNAi vector. Overexpression or constitutive activation of Rhob in RAW-GR(K) and RAW264.7 cells by transfection with wild-type Rhob expression vector (Rhob-wt) or constitutively activated Rhob plasmid (Rhob-V14) resulted in decreased proliferation of the two cell lines. Oppositely, the proliferation of RAW264.7 cells was significantly increased when the expression of Rhob by RNA interference technique or the activity of Rhob by transfection with dominant negative Rhob mutant that is defective in nucleotide binding (Rhob-N19) was inhibited. In addition, enhanced activity of Akt, but not MAPK3/1 or MAPK14, was found in RAW-GR(K) cells. Blocking the pathway of phosphatidylinositol 3-kinase (PI3K)/Akt with the specific inhibitor LY294002 decreased the proliferation and elevated RHOB protein level, indicating that PI3K/Akt signal plays its role of proliferation modulation upstream of RHOB protein. In conclusion, these results demonstrate that Rhob plays an important role in the antiproliferative effect of GR on RAW264.7 cells by GR/Akt/Rhob signaling and Rhob negatively regulates the proliferation of RAW264.7 cells.

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Expression and role of functional glucocorticoid receptors in the human androgen-independent prostate cancer cell line, DU145

Cited by 23 publications

References 23 publications

Downregulation of 15-lipoxygenase 2 by glucocorticoid receptor in prostate cancer cells

Downregulation of 15-lipoxygenase 2 by glucocorticoid receptor in prostate cancer cells

Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells

Role of RHOB in the antiproliferative effect of glucocorticoid receptor on macrophage RAW264.7 cells

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