COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

Glynn, Sharon A.; Prueitt, Robyn L.; Ridnour, Lisa A.; Boersma, Brenda J.; Dorsey, Tiffany; Wink, David A.; Goodman, Julie E.; Yfantis, Harris G.; Lee, Dong H; Ambs, Stefan

doi:10.1186/1471-2407-10-626

Cited by 65 publications

(95 citation statements)

References 32 publications

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“…It is thought that in ER positive cancers, COX-2 induces aromatase production leading to estrogen availability to drive cancer growth through the ER [75]. In ER negative cancers, COX-2 may drive cancer growth via AKT pathway activation [76]. Thus despite the differences in signaling pathways responsible for COX-2 expression, this expression appears to be a constant feature in breast cancer of increasing stage, and as mentioned earlier, a predictor of poor survival.…”

Section: Cox-2 and The Ermentioning

confidence: 93%

“…Additionally, HIF1-α can induce COX-2 directly [144] and thus may 'take over' from c-Myb. In the absence of the ER, COX-2 may continue to drive tumor growth via Akt pathway activation [76]. Given that COX-2 is implicated in an EMT featuring Snail1 and Zeb1, as outlined earlier, COX-2 and HIF1-α may work synergistically to amplify Snail1 and Zeb1 induction, resulting in robust EMT facilitating motility and invasion, and metastasis (Fig.…”

Section: Putative C-myb-cox2 Pathwaymentioning

confidence: 94%

See 1 more Smart Citation

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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Section: Cox-2 and The Ermentioning

confidence: 93%

Section: Putative C-myb-cox2 Pathwaymentioning

confidence: 94%

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

show abstract

“…Celecoxib or SC-560 treatment alone demonstrated a significantly prolonged mean survival time and MST in comparison with the control group in vivo. Recent clinical studies have provided convincing evidence of poor survival in patients who demonstrated high COX-2 expression in stage IIB cervical adenocarcinoma and breast cancer (16,17). Erkinheimo et al (18) suggested that elevated expression of COX-2 is associated with reduced survival in serous ovarian carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Effects of cyclooxygenase inhibitors on survival time in ovarian cancer xenograft-bearing mice

Zhang

et al. 2012

Oncology Letters

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Abstract. The present study was designed to investigate whether cyclooxygenase (COX) inhibitors (coxibs) could prolong survival time by attenuating the tumor growth of ovarian cancer xenograft-bearing mice. Tumor growth and survival time were observed and compared in mice which were treated with a COX-1 inhibitor (SC-560) and a COX-2 inhibitor (celecoxib) every other day for a 21 day period from the day of tumor formation. The trial lasted a total of 121 days. The combination therapy resulted in statistically significant inhibition of tumor size compared with the control group (P<0.05). Additionally, single treatment of SC-560 or celecoxib significantly prolonged the mean survival time of mice compared with the control group (P<0.05). We suggest that COX-1 and COX-2 inhibitors may improve survival and inhibit tumor growth, and that the tumor growth inhibition by coxibs may be the contributing factor for the prolonged survival time in mouse xenograft models.

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“…Among the gene products involved in the induction of the inflammatory process, Cyclooxygenase 2 (COX-2) has been shown to have a close relationship with carcinogenesis (De Marzo et al 2007;Glynn et al 2010;Gupta et al 2007;Subbaramaiah and Dannenberg 2003;Wang and DuBois 2007;Yoshinaga et al 2011). The mechanisms that underlie the tumorigenic effects of COX-2 include the inhibition of apoptosis, an increased metastatic potential, and angiogenesis via VEGF upregulation.…”

Section: Introductionmentioning

confidence: 98%

Cyclooxygenase-2 expression in central giant cell lesion of the jaws: an immunohistochemical study

et al. 2011

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Central Giant Cell Lesion (CGCL) is an uncommon benign jaw lesion, with uncertain etiology, and a variable clinical behavior. Studies of molecular markers of CGCL, may help understanding better the nature and behavior of this lesion, and eventually may represent a definitive target to pharmacological approach in the treatment of CGCL. Chronic inflammation has been found to mediate a wide variety of diseases including neoplasms. Among the gene products involved in the induction of the inflammatory process, Cyclooxygenase 2 (COX-2) has been shown to have a close relationship with tumorigenesis, however COX-2 expression has never been evaluated in CGCL. The aim of the study was to investigate the expression of COX-2 in CGCL. Immunohistochemical assessment for COX-2 expression was performed in 18 patients previously diagnosed with CGCL. Multinucleated giant cells (MGC) and mononucleated stromal cells (MSC) were used in the slide analysis. Among the patients studied, 10 were male and 8 were female, with a median age of 15.4 years. Lesions in the mandible were observed in 11 cases and 7 were found in the maxilla. There were 9 aggressive and 9 non-aggressive CGCLs. COX-2 immunopositivity was present in only 3 cases stained in both MGC and MSC. All 3 cases presented with ulcerations in the mucosa lesion, suggesting that the COX-2 expression is due to the presence of inflammation. This study does not support the involvement of COX-2 in the etiophatogenesis of CGCL.

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COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

Cited by 65 publications

References 32 publications

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Effects of cyclooxygenase inhibitors on survival time in ovarian cancer xenograft-bearing mice

Cyclooxygenase-2 expression in central giant cell lesion of the jaws: an immunohistochemical study

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