Retinoid and thiazolidinedione therapies in melanoma: an analysis of differential response based on nuclear hormone receptor expression

Klopper, Joshua; Sharma, Vibha; Berenz, Andrew; Hays, William R.; Loi, Michele; Pugazhenthi, Umarani; Said, Sherif; Haugen, Bryan R.

doi:10.1186/1476-4598-8-16

Cited by 19 publications

(34 citation statements)

References 29 publications

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“…We have previously shown that decreasing RXR γ by shRXR γ in A375(DRO) decreases response to rexinoid, TZD, and the combination [8]. Modulators of retinoid receptors have been described in melanoma and include HSP 90 and Cyclophilin B [24], but we were unable to find any direct link between S100A2 expression and RXR regulation.…”

Section: Discussionmentioning

confidence: 62%

“…We have previously demonstrated that, in A375(DRO), the combination of LGD1069 and ROSI synergistically decreases in vitro cell proliferation and in vivo tumor growth [5, 8]. Our data indicates that S100A2 is necessary to mediate the antiproliferative effects of rexinoid and TZD treatment but is not sufficient to mediate this effect.…”

Section: Discussionmentioning

confidence: 65%

“…Additionally, we have shown that RXR and PPAR γ receptors are necessary for optimal response to rexinoid or TZD therapies, as knock down of either receptor attenuates the antiproliferative response to its own ligand alone or the ligand of its heterodimer partner [8]. …”

Section: Introductionmentioning

confidence: 99%

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Combination PPARγand RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2

et al. 2010

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Nuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD) treatment in vitro and in vivo. We performed microarray analysis of A375(DRO) after TZD and combination rexinoid/TZD treatment in which the calcium binding protein S100A2 had increased expression after rexinoid or TZD treatment and a synergistic increase to combination treatment. Increased S100A2 expression is dependent on an intact PPARγ receptor, but it is not sufficient to mediate the antiproliferative effects of rexinoid/TZD treatment. Over expression of S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of S100A2 expression attenuated the response to rexinoid/TZD treatment, suggesting that S100A2 is necessary for optimal response to RXR and PPARγ activation by respective ligands. In summary, we have identified potential downstream mediators of rexinoid and TZD treatment in a poorly differentiated melanoma and found that alterations in S100A2 expression affect RXR and PPARγ signaling in A375(DRO) cells. These studies provide insight into potential mechanisms of tumor response or resistance to these novel therapies.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 65%

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Combination PPARγand RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2

et al. 2010

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“…Bexarotene was also shown to suppress both estrogen-dependent and estrogen-independent tumor development in mouse models [216,217]. In another study, using mouse xenograft models with human melanoma cell lines, bexarotene was tested alone or in combination with TTNPB or rosiglitazone (a PPARc agonist) for the treatment of melanoma and was shown to be able to reduce tumor size [218].…”

Section: Retinoids In Disease and Therapymentioning

confidence: 99%

From carrot to clinic: an overview of the retinoic acid signaling pathway

Theodosiou

Laudet

Schubert

2010

Cell. Mol. Life Sci.

284

247

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Vitamin A is essential for the formation and maintenance of many body tissues. It is also important for embryonic growth and development and can act as a teratogen at critical periods of development. Retinoic acid (RA) is the biologically active form of vitamin A and its signaling is mediated by the RA and retinoid X receptors. In addition to its role as an important molecule during development, RA has also been implicated in clinical applications, both as a potential anti-tumor agent as well as for the treatment of skin diseases. This review presents an overview of how dietary retinoids are converted to RA, hence presenting the major players in RA metabolism and signaling, and highlights examples of treatment applications of retinoids. Moreover, we discuss the origin and diversification of the retinoid pathway, which are important factors for understanding the evolution of ligand-specificity among retinoid receptors.

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“…Follicular destruction and hair cycling defects, epidermal hyperplasia [86,87] Growth and invasion arrest by NR ligands [164] AD TSLP derepression and Th2-type inflammation [88,90] Growth arrest by NR ligands [165,166,172]…”

Section: Alopeciamentioning

confidence: 99%

Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis

Hyter

Indra

2013

FEBS Letters

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Edited by Laszlo NagyKeywords: Skin Keratinocyte Melanocyte Homeostasis Type II nuclear hormone receptor Signaling Melanoma Atopic dermatitis Inflammation SCC BCC a b s t r a c t Skin homeostasis is maintained, in part, through regulation of gene expression orchestrated by type II nuclear hormone receptors in a cell and context specific manner. This group of transcriptional regulators is implicated in various cellular processes including epidermal proliferation, differentiation, permeability barrier formation, follicular cycling and inflammatory responses. Endogenous ligands for the receptors regulate actions during skin development and maintenance of tissue homeostasis. Type II nuclear receptor signaling is also important for cellular crosstalk between multiple cell types in the skin. Overall, these nuclear receptors are critical players in keratinocyte and melanocyte biology and present targets for cutaneous disease management.

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Retinoid and thiazolidinedione therapies in melanoma: an analysis of differential response based on nuclear hormone receptor expression

Abstract: Background: Metastatic melanoma has a high mortality rate and suboptimal therapeutic options. Molecular targeting may be beneficial using the rexinoid LGD1069, a retinoid × receptor selective agonist, and thiazolidinediones (TZD), PPAR selective ligands, as novel treatments.

Cited by 19 publications

References 29 publications

Combination PPARγand RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2

Combination PPARγand RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2

From carrot to clinic: an overview of the retinoic acid signaling pathway

Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis

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