Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15-Deoxy-Δ12,14-prostaglandin J2 and the Precursors in Leukemia Cell Line THP-1

Azuma, Yasutaka; Watanabe, Kyoko; Date, Masataka; Daito, Michiharu; Ohura, Kiyoshi

doi:10.1254/jphs.94.261

Cited by 18 publications

(11 citation statements)

References 39 publications

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“…In breast cancer, p21 and p27 have received considerable attention as clinical indicators and potential targets in therapeutic development (28)(29)(30). In agreement with the findings we present here, previous work in leukemia showed that impaired MKK3 signals enhanced prostaglandin PGJ2-induced proliferation, and described impaired p21 and p27 expression in treated THP-1 cells (35). In addition, a natural fungal product (FTY720) induced MKK3 activity and p21 expression in prostate cancer cells, leading to cell-cycle arrest (36), whereas studies in muscle cell differentiation have shown that dominant negative MKK3 inhibits p21 and p27 expression (37).…”

Section: Discussionsupporting

confidence: 91%

MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

et al. 2014

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Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor-suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here, we show that the mitogen-activated protein kinase (MAPK) MKK3 suppresses the growth of breast cancer, in which it varies in copy number. A pervasive loss of MKK3 gene copy number in patients with breast cancer is associated with an impairment of MKK3 expression and protein level in malignant tissues. To assess the functional role of MKK3 in breast cancer, we showed in an animal model that MKK3 activity is required for suppression of tumor growth. Active MKK3 enhanced expression of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27 Kip1 , leading to increased cell-cycle arrest in G 1 phase of the cell cycle. Our results reveal the functional significance of MKK3 as a tumor suppressor and improve understanding of the dynamic role of the MAPK pathway in tumor progression. Cancer Res; 74(1); 162-72. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 91%

MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

et al. 2014

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“…However, recent studies revealed that both PGD 2 and 15d-PGJ(2) appear to possess not only anti-inflammatory activities but also a proinflammatory potential depending on its concentration and the activation state of the target cell. For instance, PGD 2 or 15dPGJ2 stimulated the proliferation in the leukocyte cell line THP-1 at lower concentrations, whereas they inhibited the proliferation through the induction of apoptosis at high concentrations (3). In addition to the immune system, 15dPGJ 2 is suggested to play proinflammatory roles by inducing apoptosis of several human epithelial cell lines, including gastric, lung, colon, prostate, and breast.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis

Hokari

Kurihara

Nagata³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Miura S. Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis. Am J Physiol Gastrointest Liver Physiol 300: G401-G408, 2011. First published December 16, 2010 doi:10.1152/ajpgi.00351.2010.-The pathogenesis of ulcerative colitis (UC) is unclear, but enhancement of disease activity by usage of nonsteroidal anti-inflammatory drugs suggests involvement of prostanoid in its pathophysiology. However, biological effect of prostaglandin (PG) D2 on intestinal inflammation remains unknown. We investigated the expression of enzymes for PGD2 synthesis, prostaglandin D synthase (PGDS), and its relation to the activity of colitis in UC patients. The role of lipocalin-type PGDS (L-PGDS) using a murine colitis model was also assessed. Tissue samples were obtained by colonic biopsies from patients with UC. Expression levels of mRNAs for L-PGDS and hematopoietic-type PGDS were investigated by quantitative RT-PCR. COX-2 and L-PGDS expression was investigated by immunohistochemistry. Localization of L-PGDS expression was also determined by in situ hybridization. In experimental study, mice were treated with dextran sodium sulfate in the drinking water to induce colitis. The degree of colonic inflammation was compared with L-PGDS Ϫ/Ϫ mice and control mice. The level of L-PGDS mRNA expression was increased in UC patients in parallel with disease activity. Colocalization of L-PGDS and cyclooxygenase (COX) 2 was observed in lamina proprial infiltrating cells and muscularis mucosa in UC patients. The level of hematopoietic PGDS mRNA expression did not differ from control mucosa. Dextran sodium sulfate treatment to L-PGDS Ϫ/Ϫ mice showed lower disease activity than control mice. We reported for the first time the presence of L-PGDS in the COX-2-expressing cells in the mucosa of active UC patients and that only L-PGDS increased with disease activity. An animal model study suggests that PGD 2 derived from L-PGDSexpressing cells plays proinflammatory roles in colitis. prostaglandin D2; dextran sodium sulfate; chemoattractant receptorhomologous molecule expressed on Th2 cells; ulcerative colitis THE PATHOGENESIS OF ULCERATIVE colitis (UC) is unclear, but enhancement of disease activity by usage of cyclooxygenase (COX) inhibitor suggests involvement of prostanoid in its pathophysiology (10,11). In an animal model of colitis, administration of nonsteroidal anti-inflammatory dugs to IL-10

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“…The generation of 15d-PGJ 2 has been reported to increase under inflammatory conditions associated with COX-2 induction (Gilroy et al, 1999 2008). Thus, 15d-PGJ 2 potentiates mouse skin tumor formation (Millan et al, 2006), accelerates the proliferation of leukemia cells (Azuma et al, 2004) and colorectal cancer cells (Chinery et al, 1999) and has a capability to induce angiogenesis (Chinery et al, 1999;Azuma et al, 2004). Correlation between COX-2 expression and p53 accumulation has been suggested in human cancer tissues (Biramijamal et al, 2001;Leung et al, 2001;Shigemasa et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

15-Deoxy-Δ12,14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue

Kim

et al. 2010

Oncogene

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15-Deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ 2 led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ 2 directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ 2 . 9,10-Dihydro-15-deoxy-D 12,14 -prostaglandin J 2 lacking the electrophilic a,b-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [ 35 S]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ 2 . The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ 2 . Likewise, p53 binding activity of biotinylated 15d-PGJ 2 was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ 2 can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation.

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Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15-Deoxy-Δ12,14-prostaglandin J2 and the Precursors in Leukemia Cell Line THP-1

Cited by 18 publications

References 39 publications

MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis

15-Deoxy-Δ12,14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue

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