Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway

Unoki, Motoko; Nakamura, Yusuke

doi:10.1038/sj.onc.1204608

Cited by 326 publications

(277 citation statements)

References 28 publications

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“…The FOS pathway is also directly associated with genes in the network with the early growth response gene-2 (EGR2) nodal gene, which is co-regulated with EGR1. EGR2 suppressed the growth of cancer cells significantly [80] and might mediate the growth suppressive effect of the protein called phosphate and tensin homology (PTEN) [80].…”

Section: Low-dose Functions and Network Associated With Membranes Omentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues.Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of ~80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

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Section: Low-dose Functions and Network Associated With Membranes Omentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…The PINK1 gene is ubiquitously transcribed and encodes a mitochondrial kinase. 35,36 Preliminary data have suggested that PINK1 may play a role in protecting cells against stress conditions that affect mitochondrial membrane potential, 35 but the downstream targets through which PINK1 mediates its protection have not been identified. These data are derived from overexpression of mutant PINK1 in neuroblastoma cells that showed a lower membrane potential and increased cell death following exposure to a proteasomal inhibitor.…”

Section: Pink1 Mutationsmentioning

confidence: 99%

Mitochondrial dysfunction in Parkinson's disease

2007

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“…This observation is consistent with 2 previous studies investigating the expression of MKP-1 in a limited set of ovarian carcinomas. Unoki et al 19 reported a reduction of MKP-1 expression in 8 ovarian carcinomas compared to corresponding normal tissue using RT-PCR. Similarly, Ono et al 20 found a downregulation of MKP-1 mRNA by cDNA microarray in 9 of 9 ovarian carcinomas compared to non-cancerous ovarian tissue.…”

Section: Induction Of Mkp-1 Mrna By Cisplatinmentioning

confidence: 99%

Expression of mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) in primary human ovarian carcinoma

Denkert

Schmitt

Berger

et al. 2002

Intl Journal of Cancer

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The mitogen-activated protein kinase phosphatase-1, MKP-1 (CL100) is involved in inactivation of MAP-kinase pathways, regulation of stress-responses and suppression of apoptosis. We investigated expression of MKP-1 in 90 cases of primary ovarian tumors, 11 normal ovaries as well as 4 ovarian carcinoma cell lines. Immunohistochemical expression of MKP-1 protein was reduced in tissue from LMP tumors and invasive ovarian carcinomas compared to normal ovaries and cystadenomas. A moderate to strong expression of MKP-1 was detected in 57.6% of invasive ovarian carcinomas. In a descriptive univariate survival analysis, MKP-1 expression was a prognostic marker for shorter progressionfree survival of patients with invasive ovarian carcinomas. Patients with carcinomas positive for MKP-1 had a median progression-free survival of only 18.3 months compared to 40.6 months for patients with carcinomas negative for MKP-1 (log-rank test, p ‫؍‬ 0.019). Other prognostic parameters for progression-free survival were FIGO stage, grade and pT stage. In an exploratory multivariate analysis, we found that MKP-1 expression as well as FIGO stage and grade were independent prognostic factors for progression-free survival. In contrast to progression-free survival, we did not find any influence of MKP-1 expression on patient overall survival. We investigated expression and regulation of MKP-1 mRNA by Northern Blot in vitro using 4 ovarian carcinoma cell lines (SKOV-3, OVCAR-3, CAOV-3, OAW-42). MKP-1 mRNA was inducible by interleukin-1␤ and tumor necrosis factor-␣ in SKOV-3 and OVCAR-3 cells, whereas CAOV-3 and OAW-42 expressed MKP-1 mRNA constitutively. In OVCAR-3 cells MKP-1 mRNA levels were strongly inducible upon treatment of cells with cisplatin. Our data indicate that MKP-1 is expressed in a subset of ovarian carcinomas and regulated by inflammatory mediators. Expression of MKP-1 may be associated with shorter progression-free survival times. Further studies are needed to determine whether MKP-1 expression is a clinically useful marker to estimate patient prognosis as well as the response to chemotherapy.

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Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway

Cited by 326 publications

References 28 publications

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Mitochondrial dysfunction in Parkinson's disease

Expression of mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) in primary human ovarian carcinoma

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