The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

Yu, Shengqiang; Lai, Kuo-Pao; Xia, Shujie; Chang, Hong-Chiang; Chang, Chawnshang; Yeh, Shuyuan

doi:10.1038/aja.2008.44

Cited by 27 publications

(17 citation statements)

References 77 publications

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“…In hormone-free media, PC3-AR NLSTBRL1 cells showed a slightly increased growth rate compared to PC3-AR control cells (Supplemental Figure 6A) similar to what we observed in PC3-NLSTBLR1 cells in androgen media (Figure 5A). Although AR transfected PC-3 cells lines primarily show a negative growth response to androgen (Garcia-Arenas, et al 1995; Yuan et al 1993), more recently it has been observed that the level of AR expression can modulate the androgen response in these cells (Altuwaijri, et al 2007; Yu, et al 2009). The PC3-AR cell line used in our experiments showed a slight increase in growth rate upon stimulation with 10 nM R1881 compared to hormone free media (Supplemental Figure 6B).…”

Section: Resultsmentioning

confidence: 99%

TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth

Daniels¹,

Li²,

Gellert³

et al. 2013

Endocrine-Related Cancer

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Androgen Receptor (AR), a steroid hormone receptor, is critical for prostate cancer growth. However, activation of AR by androgens can also lead to growth suppression and differentiation. Transcriptional cofactors play an important role in this switch between proliferative and anti-proliferative AR target gene programs. TBLR1, a core component of the nuclear receptor corepressor (NCoR) complex, shows both co-repressor and co-activator activities on nuclear receptors, but little is known about its effects on AR and prostate cancer. We characterized TBLR1 as a coactivator of AR in prostate cancer cells and the activation is both phosphorylation and 19S proteosome dependent. We showed that TBLR1 physically interacts with AR and directly occupies the androgen response elements of affected AR target genes in an androgen-dependent manner. TBLR1 is primarily localized in the nucleus in benign prostate cells and nuclear expression is significantly reduced in prostate cancer cells in culture. Similarly, in human tumor samples, the expression of TBLR1 in the nucleus is significantly reduced in the malignant glands compared to the surrounding benign prostatic glands (p<0.005). Stable ectopic expression of nuclear TBLR1 leads to androgen-dependent growth suppression of prostate cancer cells in vitro and in vivo by selective activation of androgen regulated genes associated with differentiation (e.g. KRT18) and growth suppression (e.g. NKX3.1), but not cell proliferation of the prostate. Understanding the molecular switches involved in the transition from AR dependent growth promotion to AR dependent growth suppression will lead to more successful prostate cancer treatments.

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Section: Resultsmentioning

confidence: 99%

TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth

Daniels¹,

Li²,

Gellert³

et al. 2013

Endocrine-Related Cancer

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“…This is surprising, as the PC3, DU145 and LNCaP cell lines express ghrelin and GHSR1a and ghrelin treatment stimulates cell proliferation in these cell lines [16,18]. The different response may be due to the fact that the three prostate cancer cell lines treated with ghrelin are of different metastatic origins [50]. The PC3 prostate cancer cell line is derived from a bone metastasis, the DU145 cell line is derived from a brain metastasis and the LNCaP prostate cancer cell line is derived from a lymph node metastasis.…”

Section: Resultsmentioning

confidence: 99%

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Seim

Jeffery

Amorim

et al. 2013

Reprod Biol Endocrinol

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BackgroundGhrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified.MethodsWe used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR.ResultsWe have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines.ConclusionsThis study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

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“…In order to study PCa, a variety of cell lines mimicking androgen-dependent and androgen-independent carcinogenic formations have been extensively used [28]. These cell lines have enabled researchers to directly test a series of antitumor drug candidates, such as tumor apoptosis inducers [29] or enhancers of antitumor immune response [30], as well as to evaluate the genomic foundations of PCa [31] and to further decipher the biological characteristics within cancer development [32, 33].…”

Section: Introductionmentioning

confidence: 99%

Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer

et al. 2013

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Prostate cancer (PCa) is one of the most common malignancies found in males. The development of PCa involves several mutations in prostate epithelial cells, usually linked to developmental changes, such as enhanced resistance to apoptotic death, constitutive proliferation, and, in some cases, to differentiation into an androgen deprivation-resistant phenotype, leading to the appearance of castration-resistant PCa (CRPCa), which leads to a poor prognosis in patients. In this review, we summarize recent findings concerning the main deregulations into signaling pathways that will lead to the development of PCa and/or CRPCa. Key mutations in some pathway molecules are often linked to a higher prevalence of PCa, by directly affecting the respective cascade and, in some cases, by deregulating a cross-talk node or junction along the pathways. We also discuss the possible environmental and nonenvironmental inducers for these mutations, as well as the potential therapeutic strategies targeting these signaling pathways. A better understanding of how some risk factors induce deregulation of these signaling pathways, as well as how these deregulated pathways affect the development of PCa and CRPCa, will further help in the development of new treatments and prevention strategies for this disease.

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The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

Cited by 27 publications

References 77 publications

TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth

TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer

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