Triiodothyronine modulates cell proliferation of human prostatic carcinoma cells by downregulation of the B‐Cell translocation gene 2

Tsui, Ke-Hung; Hsieh, W.C.; Lin, Meng‐Chih; Chang, Phei‐Lang; Juang, Horng‐Heng

doi:10.1002/pros.20725

Cited by 61 publications

(67 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides their suppressor role, TRs enhanced tumor progression in other studies. Thyroid hormones stimulate the proliferation of several cancer cell types including those from the pituitary (Barrera-Hernandez et al, 1999), gliomas (Davis et al, 2006), breast cancers (Hall et al, 2008) and prostate cancers (Tsui et al, 2008). Thyroid hormone and the TRa1 receptor control epithelial cell proliferation and the expression of components of the Wnt pathway (Plateroti et al, 2006).…”

Section: Trb1mentioning

confidence: 99%

Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

Huang

Yeh

et al. 2011

Oncogene

View full text Add to dashboard Cite

Thyroid hormone, 3, 3 0 , 5-triiodo-L-thyronine (T 3 ), mediates cell growth, development and differentiation by binding to its nuclear receptors (TRs). The role of TRs in cancer is still undefined. Notably, hyperthyroxinemia has been reported to influence the rate of colon cancer in an experimental model of carcinogenesis in rats. Previous microarray analysis revealed that cathepsin H (CTSH) is upregulated by T 3 in HepG2-TR cells. We verified that mRNA and protein expression of CTSH are induced by T 3 in HepG2-TR cells and in thyroidectomized rats following administration of T 3 . The possible thyroid hormone-responsive elements of the CTSH promoter localized to the nucleotides -2038 to -1966 and -1565 to -1501 regions. An in vitro functional assay showed that CTSH can increase metastasis. J7 cells overexpressing CTSH were inoculated into severe combined immunedeficient mice and these J7-CTSH mice displayed a greater metastatic potential than did J7-control mice. The clinicopathologic significance of CTSH expression in hepatocellular carcinoma (HCC) was also investigated. The CTSH overexpressing in HCC was associated with the presence of microvascular invasion (P ¼ 0.037). The microvascular invasion characteristic is closely related to our in vitro characterization of CTSH function. Our results show that T 3 -mediated upregulation of CTSH led to matrix metallopeptidase or extracellular signal-regulated kinase activation and increased cell migration. This study demonstrated that CTSH overexpression in a subset hepatoma may be TR dependent and suggests that this overexpression has an important role in hepatoma progression.

show abstract

Section: Trb1mentioning

confidence: 99%

Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

Huang

Yeh

et al. 2011

Oncogene

View full text Add to dashboard Cite

show abstract

“…Studies are necessary to understand the bidirectional effects of T3 and ARA70. The reduced tumor growth associated with T3 could be explained by indirect mechanisms, because in vitro studies show that T3 directly increases cell proliferation by decreasing the expression of a p53 target, the B-cell translocation protein (28,62). Additional studies are required to understand the direct or indirect effects of T3 on tumor prostate growth.…”

Section: Discussionmentioning

confidence: 99%

“…LNCaP and DU145 cells were treated for 6 and 4 d, respectively, with ISO (50 μmol/L), T3 (10 nmol/L), T4 (100 nmol/L), ISO + T3 or ISO + T4. The selected doses and times were based on previous assays (8,28,34). In both cell types, the number and length of neurite-like projections were measured in four random fields of non-clustered cells.…”

Section: Balb/c Nude Mice and Lncap Tumor Inductionmentioning

confidence: 99%

Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation

Delgado‐González

Sánchez-Tusié

Morales

et al. 2016

Mol Med

View full text Add to dashboard Cite

Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established that β-adrenergic activation (protein kinase A [PKA]/cAMP response element binding protein [CREB]) promotes cancer progression, but the role of thyroid hormones is poorly understood. We analyzed the effects of β-adrenergic stimulation (isoproterenol [ISO]) and/or thyroid hormone on neuroendocrine (NE) differentiation and cell invasion, using in vivo (LNCaP tumor) and in vitro models (LNCaP and DU145 human cells). Nude mice were inoculated with LNCaP cells and were treated for 6 wks with ISO (200 μg/d), triiodothyronine (T3, 2.5 μg/d) or both. ISO alone reduced tumor growth but increased tumor expression of cAMP response element (CRE)-dependent genes (real-time polymerase chain reaction, chromogranin A, neuron-specific enolase, survivin, vascular endothelial growth factor [VEGF], urokinase plasmin activator [uPA] and metalloproteinase-9 [MMP-9]) and some proteins related to NE differentiation and/or invasiveness (synaptophysin, VEGF, pCREB). T3 reduced tumor growth and prevented the overexpression of ISO-stimulated factors through a pCREB-independent mechanism. In low invasive LNCaP cells, 50 μmol/L ISO or 100 nmol/L thyroxine (T4) induced the acquisition of NE-like morphology (phase-contrast microscopy), increased VEGF secretion (ELISA) and invasive capacity (Transwell assay), but no synergistic effects were observed after the coadministration of ISO + T4. In contrast, 10 nmol/L T3 alone had no effect, but it prevented the NE-like morphology and invasiveness stimulated by ISO. None of these treatments had any effect on highly invasive DU145 cells. In summary, this study showed that ISO and T4 increase cancer progression, and T3 attenuates ISO-stimulated progression. Further studies are required to determine if changes in the ratio of T4/T3 could be relevant for prostate cancer progression.

show abstract

“…However, despite this, it has only been since the mid-90s that we have become aware of the importance of androgen signalling in prostate progression. This was on the basis of improving technology, which allowed for the detection of AR in relapsed tumours in metastatic sites (van der Kwast et al 1991, Hobisch et al 1995. This also prompted widespread adoption of the term castrate-resistant prostate cancer (CRPC), as opposed to androgen-independent disease.…”

Section: Androgen Receptor (Ar or Nr3c4)mentioning

confidence: 99%

“…anti-proliferative genes (Hsieh & Juang 2005, Tsui et al 2008. THR signalling has also been suggested to have a pro-tumourigenetic effect through the regulation of cytokines (Ding et al 2015a,b) as well as regulation of the proto-oncogene c-FOS (Martinez et al 2000).…”

Section: :11mentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

Leach

Powell

Bevan

2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease -hence the quest for new effective therapies for 'castrate-resistant' prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC, other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence, the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This review aims to provide a snapshot of the current knowledge of the roles of different nuclear receptors in prostate cancer -a rapidly evolving field of research.

show abstract

Triiodothyronine modulates cell proliferation of human prostatic carcinoma cells by downregulation of the B‐Cell translocation gene 2

Abstract: These results suggested that the T3 upregulates proliferation of LNCaP cells by downregulating BTG2 gene expression through the consensus TRE pathway.

Cited by 61 publications

References 47 publications

Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

Contact Info

Product

Resources

About