Specific induction of <i>gadd45</i> in human melanocytes and melanoma cells after UVB irradiation

Pedeux, Rémy; Lefort, Karine; Cuenin, Cyrille; Cortes, Ulrich; Kellner, Karine; Doré, Jean‐François; Nakazawa, Hisayoshi

doi:10.1002/ijc.10275

Cited by 23 publications

(22 citation statements)

References 24 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,7 Since other studies have shown that UVB can induce G 2 arrest of melanocytes and melanoma cells [2][3][4][5] and that, in other models, Gadd45a could play a role in G 2 arrest, 14,15,26 we undertook the analysis of Gadd45a involvement in the UVB induced cell cycle arrest of melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…1 However, G 2 cell cycle arrest seems to be characteristic of the response of normal human melanocytes and melanoma cells to UVB. [2][3][4][5] We previously showed that UVB irradiation of melanocytes and melanoma cells induces Gadd45a expression through an original, p53-independent pathway, 6 involving the specific upregulation of GADD45A expression by the POU family gene product N-Oct3. 7 GADD45A is one of several Growth-Arrest and DNA-Damage-inducible genes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles

Fayolle¹,

Pourchet²,

Cohen³

et al. 2006

Cell Cycle

Self Cite

View full text Add to dashboard Cite

Exposure to solar UVB radiation is involved in the development of cutaneous melanoma. We previously showed that human melanocytes and melanoma cells respond to UVB radiation via a p53-independent pathway involving GADD45A activation. Here, we determined that UVB-induction of Gadd45a is necessary for G 2 arrest and that Gadd45a and its partner p21 Waf1 colocalize in nuclear bodies called Nuclear Speckles. We further observed that UVB-induced G 2 arrest is associated with Cdc2 accumulation in these Nuclear Speckles. Knock-down of Gadd45a expression by RNA interference prevents both UVB-induced Cdc2 accumulation in Nuclear Speckles and G 2 arrest. Our results demonstrate that UVB-induced G 2 arrest of melanoma cells is Gadd45a-dependent. Furthermore, we show that Cdc2 sequestration by Gadd45a occurs in Nuclear Speckles, suggesting a new role for these nuclear bodies, so far only linked to RNA maturation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles

Fayolle¹,

Pourchet²,

Cohen³

et al. 2006

Cell Cycle

Self Cite

View full text Add to dashboard Cite

show abstract

“…PCR primers for human GADD45A have sequences: 5Ј primer, 5Ј-ACA GAA ACT GAT GCC AAG GG-3Ј, and 3Ј primer, 5Ј-TTT TCC TTC CTG CAT GGT TC-3Ј. 24 The annealing temperature of 54°C was used.…”

Section: Reverse-transcription Polymerase Chain Reactionmentioning

confidence: 99%

Retinoids and Pulmonary Hypertension

et al. 2005

View full text Add to dashboard Cite

Background-Retinoic acid has antimitogenic effects on smooth muscle cells. Studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension and the effects of retinoic acid on human pulmonary artery smooth muscle cell growth. Methods and Results-We measured retinoid levels by gas chromatograph-mass spectrometer technique in plasma of idiopathic pulmonary arterial hypertension patients and in age-and sex-matched healthy control subjects. Patients had significantly lower levels of all-trans retinoic acid and 13-cis retinoic acid than control subjects but similar 9-cis retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-trans retinoic acid suppressed serotonin-induced cell growth. These cells were found to express the retinoid acid receptors RAR␣, RAR␤, RAR␥, RXR␣, and RXR␤. Gene array analysis showed that retinoic acid induces the expression of GADD45A, a known cell growth suppressor. Contrary to expectations, plasma from pulmonary hypertension patients suppressed cell growth, likely influenced by factors other than retinoids. Conclusions-Idiopathic

show abstract

“…The growth arrest and DNA damage-inducible gene (GADD45) is a p53-regulated gene involved in DNA repair, which has been found to be upregulated in cells subjected to stress. 34 UV irradiation and overexpression of FGF 2 lead to the upregulation of gene GADD45. 35 The ectopic overexpression of GADD45 results in cell growth arrest and sensitization of cells to undergo apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling identifies IL‐13 receptor α2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Gonzalez-Moreno

Calvo

Joshi

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mocktransfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor ␣2 (IL-13R␣2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R␣2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R␣2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC 50 (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R␣2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38. © 2004 Wiley-Liss, Inc.Key words: cDNA microarrays; prostate cancer; adrenomedullin; IL-13R␣2; gene expression profiling Prostate carcinoma is the second leading cause of cancer mortality among men in the United States. 1 The 5-year relative survival rate for the patients whose tumors are diagnosed with local or regional disease approaches 100%, but the relative 10-and 15-year survival rates are reduced to 75% and 54%, respectively. 1 Although localized prostate cancer may be successfully treated, 70% of patients eventually progress and develop metastasis. The current nonsurgical therapeutic regimens for treating prostate carcinoma include radio-, hormonal-and chemotherapy, as well as a combination of these regimens, depending on specific circumstances of the patient. The limited success of treating particular forms of prostate cancer requires that additional targets for therapy be identified and tested.Expression of adrenomedullin, an amidated peptide that was originally isolated from human pheochromocytoma, 2 has been documented in both the human and rat prostate, 3 human prostate carcinoma 4 and prostate cancer cell lines, 4 where it has been suggested that adrenomedullin (AM) may act as an autocrine/ paracrine factor. Human AM consists of 52 amino acids (50 amino acids for rat AM) and shar...

show abstract

Specific induction of gadd45 in human melanocytes and melanoma cells after UVB irradiation

Cited by 23 publications

References 24 publications

UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles

UVB-Induced G2 Arrest of Human Melanocytes Involves Cdc2 Sequestration by Gadd45a in Nuclear Speckles

Retinoids and Pulmonary Hypertension

Gene expression profiling identifies IL‐13 receptor α2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Contact Info

Product

Resources

About