Effect of Prostaglandins on the Regulation of Tumor Growth

Ishihara, Shunji; Rumi, M.A. Karim; Okuyama, Toshihiko; Kinoshita, Yoshikazu

doi:10.2174/1568011043352902

Cited by 23 publications

(15 citation statements)

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“…In this regard, 15d-PGJ 2 has already been shown to induce apoptosis in different types of tumor cells (20,65). A good example of this action is MM, where the 15d-PGJ 2 -mediated suppression of NF-B, an antiapoptotic regulator in these cells, is responsible for this mechanism (66).…”

Section: Discussionmentioning

confidence: 99%

15-Deoxy-Δ12,14-Prostaglandin J2 Negatively Regulates rankl Gene Expression in Activated T Lymphocytes: Role of NF-κB and Early Growth Response Transcription Factors

Fionda

Nappi

Piccoli

et al. 2007

The Journal of Immunology

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Receptor activator of NF-κB ligand (RANKL) and its receptor RANK are cell surface proteins abundantly expressed in bone and lymphoid tissues, whose interaction triggers different signaling pathways leading to activation and differentiation of osteoclasts, pivotal actors of the normal bone remodeling cycle. Moreover, RANKL may act as an immunomodulator, representing an important dendritic cell survival factor produced by activated T cells. A large body of research has shown that not only does the RANKL/RANK system regulate the physiology of bone development but also plays an important pathological role in bone destruction mediated by inflammatory disorders or bone metastatic tumors. 15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a cyclopentenone-type PG endowed with anti-inflammatory properties and produced by different cells, including those of the immune system. Although 15d-PGJ2 has been studied as a natural ligand of the peroxisome proliferator-activated receptor-γ nuclear receptor, relevant peroxisome proliferator-activated receptor-γ-independent actions mediated by this prostanoid have been described. In this study, we describe the effect of 15d-PGJ2 on the expression of the rankl gene in T lymphocytes. We show that 15d-PGJ2 inhibits rankl mRNA expression, protein, and rankl promoter activity by mechanisms mediated by its chemically reactive cyclopentenone moiety. Our data also indicate that 15d-PGJ2 represses rankl activation by interfering with the expression and/or activity of the transcription factors NF-κB, early growth response-2, and early growth response-3, whose altered balancing and transactivation may contribute for the repression of this gene. These results place rankl as a novel molecular target for the different immunoregulatory activities mediated by 15d-PGJ2. The physiological and pharmacological implications of these observations are discussed.

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Section: Discussionmentioning

confidence: 99%

15-Deoxy-Δ12,14-Prostaglandin J2 Negatively Regulates rankl Gene Expression in Activated T Lymphocytes: Role of NF-κB and Early Growth Response Transcription Factors

Fionda

Nappi

Piccoli

et al. 2007

The Journal of Immunology

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“…C1P has also been reported to activate cPLA 2 , recruiting it to Golgi and plasma membranes, resulting in the cleavage of arachidonic acid that is then converted into a variety of prostaglandins. Prostaglandins have, in turn, been associated with many inflammatory processes as well as regulation of cell growth (35) and cancer (reviewed in (36)). High CERK expression has been reported to be associated with poor recurrence-free survival in women with ER-negative breast cancer (37).…”

Section: Introductionmentioning

confidence: 99%

Ceramide Kinase Promotes Tumor Cell Survival and Mammary Tumor Recurrence

et al. 2014

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Recurrent breast cancer is typically an incurable disease and, as such, is disproportionately responsible for deaths from this disease. Recurrent breast cancers arise from the pool of disseminated tumor cells (DTCs) that survive adjuvant or neoadjuvant therapy, and patients with detectable DTCs following therapy are at substantially increased risk for recurrence. Consequently, the identification of pathways that contribute to the survival of breast cancer cells following therapy could aid in the development of more effective therapies that decrease the burden of residual disease and thereby reduce the risk of breast cancer recurrence. We now report that Ceramide Kinase (Cerk) is required for mammary tumor recurrence following HER2/neu pathway inhibition and is spontaneously up-regulated during tumor recurrence in multiple genetically engineered mouse models for breast cancer. We find that Cerk is rapidly up-regulated in tumor cells following HER2/neu down-regulation or treatment with Adriamycin and that Cerk is required for tumor cell survival following HER2/neu down-regulation. Consistent with our observations in mouse models, analysis of gene expression profiles from over 2,200 patients revealed that elevated CERK expression is associated with an increased risk of recurrence in women with breast cancer. Additionally, although CERK expression is associated with aggressive subtypes of breast cancer, including those that are ER–, HER2+, basal-like, or high grade, its association with poor clinical outcome is independent of these clinicopathological variables. Together, our findings identify a functional role for Cerk in breast cancer recurrence and suggest the clinical utility of agents targeted against this pro-survival pathway.

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“…8,9) In addition, PGs also contribute to tumor growth by inducing angiogenesis and inhibiting apoptosis. 10,11) Nuclear transcription factor kappa-B (NF-kB) is one of the most important transcription factors, and is found in cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in healthy and in disease states. 12,13) The activation of NF-kB involves the phosphorylation of IkBs at two critical serine residues (Ser32, Ser36) via the IkB kinase (IKK) signalosome complex.…”

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confidence: 99%