p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis

Vasseur, Sophie; Hoffmeister, Albrecht; Garcia-Montero, Andrés; Mallo, Gustavo V.; Feil, Robert; Kühbandner, Susanne; Dagorn, Jean Charles; Iovanna, Juan

doi:10.1038/sj.onc.1205222

Cited by 80 publications

(101 citation statements)

References 36 publications

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“…NUPR1 gene expression was strongly induced by cycloheximide, TNFa, dexamethasone, ceramide, staurosporine, or serum starvation in the AR4-2J cells, a rat pancreatic tumor cell (2). NUPR1 was also upregulated upon exposure to the DNA damage agent, adriamycin, in mouse embryonic fibroblasts (MEFs) (4) and to the genotoxic stress-inducing agent, doxorubicin, in breast cancer cells (5).…”

Section: Introductionmentioning

confidence: 93%

“…It has been reported that NUPR1 increases p53 intracellular amount and transactivation capacity (4,5). Therefore, to examine the involvement of p53 in the regulation of NUPR1 expression, we measured NUPR1 mRNA levels by RT-PCR in seven lung cancer cell lines with wild and mutant p53 phenotype.…”

Section: Inhibition Of Atf4 Leads To Nupr1 Suppressionmentioning

confidence: 99%

“…Moreover, NUPR1 is expressed in various cell types in response to several cellular stress factors (2,4,5). NUPR1 gene expression was strongly induced by cycloheximide, TNFa, dexamethasone, ceramide, staurosporine, or serum starvation in the AR4-2J cells, a rat pancreatic tumor cell (2).…”

Section: Introductionmentioning

confidence: 99%

“…NUPR1 is implicated in diverse functions, including transcription regulation (6), diabetic renal mesangial cell hypertrophy (7), modulation of apoptosis (4,8), and cell cycle regulation, where the protein functions as a growth promoter (2, 9). NUPR1 overexpression is additionally associated with tumor progression (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4

et al. 2009

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SummaryNuclear protein 1 (NUPR1) was originally identified as p8, a member of the family of HMG-I/Y transcription factors induced in response to various cellular stressors. However, the signaling pathway underlying NUPR1 induction by cellular stresses remains to be established. In this study, we found that the expression of NUPR1 by various stresses induced by activating transcription factor 4 (ATF4). Loss of ATF4 using siRNA significantly diminished NUPR1 expression. Overexpression of ATF4 caused NUPR1 levels to rise. NUPR1 expression was associated with enhanced transcriptional activation of genes of ATF4 downstream, suggesting that the protein promoted the transcription of stress-regulated genes via positive feedback on the ATF4 pathway.

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Section: Introductionmentioning

confidence: 93%

Section: Inhibition Of Atf4 Leads To Nupr1 Suppressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4

et al. 2009

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“…It has also been shown that p8 is a cell growth inhibitor that facilitates apoptosis induced in fibroblasts by DNA damage. 10 The process may involve p53.…”

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confidence: 99%

Expression of Com‐1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Jiang

Watkins

Douglas-Jones

et al. 2005

Intl Journal of Cancer

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Com‐1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com‐1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n‐120) with matched normal non‐neoplastic mammary tissues (n = 32) were used. Expression of Com‐1 in cancer cells and mammary tissues were studied using conventional and real‐time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann‐Whitney U‐test and Cox Proportion analysis. Com‐1 was expressed in breast cancer cell lines. Com‐1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com‐1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com‐1, compared to normal non‐neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 ± 135 copies of Com1 transcript, 44.3 ± 36 and 0.64 ± 0.24, respectively, p = 0.06 by Kruskal‐Wallis test). Likewise, node positive tumours had low levels of Com‐1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 ± 7 copies of Com1 transcript), had local recurrence (41.5 ± 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 ± 0.03 copies of Com1 transcript) had lower levels of Com‐1, when compared to tumours from patients who remained disease free (156 ± 129 copies of Com1 transcript). There was no significant correlation between Com‐1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com‐1 in ER‐β positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow‐up 120 months). Com‐1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com‐1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com‐1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status. © 2005 Wiley‐Liss, Inc.

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Upregulation of the stress‐associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues

Plant¹,

Wang²,

Vasseur³

et al. 2005

Glia

Self Cite

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Cuprizone-induced demyelination is a mouse model of multiple sclerosis (MS) as cuprizone-fed mice exhibit neuroin-flammation and demyelination in the brain. Upon removal of cuprizone from the diet, inflammation is resolved and reparative remyelination occurs. In an Affymetrix Gene-Chip analysis, the stress-associated gene p8 was strongly upregulated (>10×) during cuprizone-induced demyelination but not remyelination. We verified this upregulation (>15×) of p8 in the CNS during demyelination by real-time polymerase chain reaction (PCR). This upregulation is brain-specific, as p8 is not elevated in the liver, lung, kidney, spleen, and heart of cuprizone-treated mice. We also localized the cellular source of p8 during cuprizone treatment, and further found elevated expression during embryogenesis but not in normal adult brain. Compared with wild-type controls, the death of oligodendrocytes in p8 −/− mice is delayed, as is microglial recruitment to areas of demyelination. The corpus callosum of p8 −/− mice demyelinates at a slower rate than wild-type mice, suggesting that p8 exacerbates CNS inflammation and demyelination. Enhanced expression of p8 is also observed in the spinal cords of mice with acute experimental autoimmune encephalomyelitis (EAE) induced by PLP 139-151 peptide (10×). Increased expression is detected during disease onset and expression wanes during the remission phase. Finally, p8 is found upregulated (8×) in post-mortem tissue from MS patients and is higher in the plaque tissue compared with adjacent normal-appearing white and gray matter. Thus, p8 is an excellent candidate as a novel biomarker of demyelination.

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p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis

Cited by 80 publications

References 36 publications

Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4

Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4

Expression of Com‐1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Upregulation of the stress‐associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues

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