Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth

Kajita, Sabine; Ruebel, Katharina H.; Casey, Mary B.; Nakamura, Nobuki; Lloyd, Ricardo V.

doi:10.1038/modpathol.3800285

Cited by 67 publications

(49 citation statements)

References 44 publications

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“…In vitro studies of thyroid cancer cell lines have shown that a selective inhibitor of COX-2, NS-398, can inhibit proliferation (13), and reduce cellular migration and invasion (14). In esophageal cancer, COX-2 expression has also been shown to be associated with anti-apoptosis (15).…”

Section: Introductionmentioning

confidence: 99%

Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of Patients Older Than 40 Years of Age

Patel

Kitahara

Park

et al. 2015

Thyroid

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Background: Cyclooxygenase (COX-2) has been associated with tumor growth and metastasis in several cancers, including thyroid cancer. For this reason, several investigators have studied COX-2 inhibitors in preclinical models of thyroid cancer and found antineoplastic effects. Thus, the primary aim of this study was to assess if the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of thyroid cancer. A second aim of the study was to determine additional risk or protective factors for thyroid cancer. Methods: Three large prospective population-based studies (the NIH-AARP Diet and Health Study; the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and the U.S. Radiologic Technologists Study) were pooled to investigate the association between self-reported frequency of aspirin and nonaspirin NSAID use one year prior to baseline (no use, £2/week, >2-6/week, and ‡7/week) and subsequent risk of thyroid cancer. A Cox regression proportional hazard model was used to estimate aggregated hazard ratios (HR) adjusted for cohort, sex, race/ ethnicity, weight, smoking status, and alcohol intake. ) were independently associated with an increased thyroid cancer risk. Current smoking status and moderate and excessive alcohol use were also confirmed as independent risk factors associated with a reduced thyroid cancer risk. Conclusions: Neither nonaspirin NSAIDs nor aspirin use is associated with a reduced risk of thyroid cancer. Women and obesity are associated with an increased risk of thyroid cancer, whereas smoking and alcohol use are associated with decreased risk of thyroid cancer.

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Section: Introductionmentioning

confidence: 99%

Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of Patients Older Than 40 Years of Age

Patel

Kitahara

Park

et al. 2015

Thyroid

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“…TxA 2 is a potent vasoconstrictor, mitogen, and platelet activator (9)(10)(11). Increased thromboxane synthase expression and/or elevated levels of TxB 2 , the stable product of TxA 2 , were found in papillary thyroid carcinoma (12), larynx squamous cell carcinoma (13), and renal carcinoma (14). Previously, we reported an increase in thromboxane synthase at mRNA level in renal carcinoma, breast carcinoma, prostate cancer, and uterine cancer when compared with their matched normal tissues in a cancer profiling array (15).…”

Section: Introductionmentioning

confidence: 99%

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

et al. 2008

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Thromboxane A 2 (TxA 2 ) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product prostaglandin H 2 as the substrate. Previously, increased expression of thromboxane synthase was found in prostate tumors, and tumor cell motility was attenuated by inhibitors of thromboxane synthase. This study was undertaken to elucidate how tumor motility is regulated by TxA 2 . Here, we report that human prostate cancer cells express functional receptors for TxA 2 (TP). Ligand binding assay found that PC-3 cells binded to SQ29548, a high-affinity TP antagonist, in a saturable manner with K d of 3.64 nmol/L and B max of 120.4 fmol per million cells. Treatment of PC-3 cells by U46619, a TP agonist, induced PC-3 cell contraction, which was blocked by pretreatment with the TP antagonist SQ29548 or pinane TxA 2 . The migration of prostate cancer cells was significantly inhibited either by sustained activation of TP or by blockade of TP activation, suggesting that TP activation must be tightly controlled during cell migration. Further studies found that small GTPase RhoA was activated by TP activation, and pretreatment of PC-3 cells with Y27632, a Rho kinase (ROCK) inhibitor, blocked U46619-induced cell contraction. A dominant-negative mutant of RhoA also blocked U46619-induced cell contraction. Taken together, the data suggest that TPs are expressed in prostate cancer and activation of TPs regulates prostate cancer cell motility and cytoskeleton reorganization through activation of Rho. [Cancer Res 2008;68(1):115-21]

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“…As the TXA 2 -TP axis has been implicated in the development of prostate and breast cancer (20,33,47,94,95), the findings herein suggest that aberrant WT1 regulation of TPα expression may contribute to such cancers and potentially to WT itself. In addition, bearing in mind that the TPα and TPβ isoforms display a number of important functional similarities but also differences in terms of their signalling (6) and regulation including in certain cancers (96,97), coupled with the fact that they are regulated by distinct promoters within the TBXA2R gene, it will be of considerable interest to investigate the expression and transcriptional regulation of TPβ in human cancers, in particular in prostate and breast cancer.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 92%

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

Kinsella

2016

Wilms Tumor

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Copyright: The Author.Licence: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the author and the publisher are explicitly identified and properly acknowledged as the original source. AbstractThe prostanoid thromboxane (TX)A 2 plays a fundamental role in vascular haemostasis and, more recently, is increasingly implicated in various neoplasms including in prostate, breast and bladder cancers, among others. In humans, TXA 2 signals through the TPα and TPβ isoforms of the T prostanoid receptor (TP), two structurally related receptors that display both common, over-lapping but also distinct, isoform-specific physiologic roles. Consistent with this, while TPα and TPβ are encoded by the same gene, the TBXA2R, they are Kinsella 164 differentially expressed due to their transcriptional regulation by distinct promoters where promoter (Prm) 1 regulates TPα expression and Prm3 regulates TPβ. While the clinical evidence for the role of the TXA 2 -TP axis in neoplastic progression is increasing, few studies to date have investigated the role of the individual TPα/TPβ isoforms in human cancer or indeed in most other diseases in which the TXA 2 -TP axis is implicated. Focusing on TPα, this review details the current understanding of the factors regulating its expression and transcriptional regulation through Prm1, including in prostate and breast cancers. Emphasis is placed on the trans-acting transcriptional regulators that bind to cis-elements within the core and upstream regulatory regions of Prm1 under basal conditions and in response to cellular differentiation. A particular focus is placed on the role of the tumour suppressor Wilms' tumour 1 in the regulation of TPα expression through Prm1 in megakaryoblastic cells of vascular origin and in prostate and breast carcinoma cells. Collectively, this review details current knowledge of the factors determining regulation of the TXA 2 -TPα axis and thereby provides a genetic basis for understanding the role of TXA 2 in the progression of certain human cancers.

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Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth

Cited by 67 publications

References 44 publications

Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of Patients Older Than 40 Years of Age

Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of Patients Older Than 40 Years of Age

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

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