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Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro.

Klein T, Benders J, Roth F, Baudler M, Siegle I, Kömhoff M - Mediators Inflamm. (2015)

Bottom Line: Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines.PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P = 0.038; n = 193).Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Philipps University, 35033 Marburg, Germany.

ABSTRACT
Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS) in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients' 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7) and a human T-cell leukemia cell line (CCRF-CEM). PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P = 0.038; n = 193). Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.

No MeSH data available.


Related in: MedlinePlus

Relationship between PGIS expression and overall survival of 193 patients. The Kaplan-Meier survival curves shown are for subgroups with either low (IRS2) or high (IRS ≥ 3) PGIS expression among all patients under study.
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fig2: Relationship between PGIS expression and overall survival of 193 patients. The Kaplan-Meier survival curves shown are for subgroups with either low (IRS2) or high (IRS ≥ 3) PGIS expression among all patients under study.

Mentions: Kaplan-Meier survival curves were created from the data of 193 patients with complete information (see Table 1) to evaluate the prognostic value of established parameters for overall survival. As expected, the classical prognostic factors, that is, histology grade, tumor size, and nodal status, were all significantly associated with overall survival, whereas age, steroid receptor status, and menopausal age were not (Table 1). To evaluate a possible relationship between PGIS expression and disease outcome, different IRS subgroups were initially defined and Kaplan-Meier analysis was performed for overall survival. In these analyses, it became apparent that subgroups with higher PGIS expression levels had shorter mean survival times than subgroups with lower expression (data not shown). This suggested the use of a single cutoff value to simplify further analyses. To select a value, the minimal P value approach was used, and cutoffs from IRS 1 to 5 were compared by Kaplan-Meier analysis. The statistical results, with and without application of the Bonferroni correction for multiple statistical testing, are listed in Table 2. The most discriminative value (IRS ≥ 3) was used for further subgroup analyses and multivariate Cox regression analysis. At 10 years following their diagnosis, 64.6% of patients with low PGIS expression (IRS < 3) were still alive compared with 36.4% in the group with high PGIS expression (IRS ≥ 3, Figure 2).


Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro.

Klein T, Benders J, Roth F, Baudler M, Siegle I, Kömhoff M - Mediators Inflamm. (2015)

Relationship between PGIS expression and overall survival of 193 patients. The Kaplan-Meier survival curves shown are for subgroups with either low (IRS2) or high (IRS ≥ 3) PGIS expression among all patients under study.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4526217&req=5

fig2: Relationship between PGIS expression and overall survival of 193 patients. The Kaplan-Meier survival curves shown are for subgroups with either low (IRS2) or high (IRS ≥ 3) PGIS expression among all patients under study.
Mentions: Kaplan-Meier survival curves were created from the data of 193 patients with complete information (see Table 1) to evaluate the prognostic value of established parameters for overall survival. As expected, the classical prognostic factors, that is, histology grade, tumor size, and nodal status, were all significantly associated with overall survival, whereas age, steroid receptor status, and menopausal age were not (Table 1). To evaluate a possible relationship between PGIS expression and disease outcome, different IRS subgroups were initially defined and Kaplan-Meier analysis was performed for overall survival. In these analyses, it became apparent that subgroups with higher PGIS expression levels had shorter mean survival times than subgroups with lower expression (data not shown). This suggested the use of a single cutoff value to simplify further analyses. To select a value, the minimal P value approach was used, and cutoffs from IRS 1 to 5 were compared by Kaplan-Meier analysis. The statistical results, with and without application of the Bonferroni correction for multiple statistical testing, are listed in Table 2. The most discriminative value (IRS ≥ 3) was used for further subgroup analyses and multivariate Cox regression analysis. At 10 years following their diagnosis, 64.6% of patients with low PGIS expression (IRS < 3) were still alive compared with 36.4% in the group with high PGIS expression (IRS ≥ 3, Figure 2).

Bottom Line: Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines.PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P = 0.038; n = 193).Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Philipps University, 35033 Marburg, Germany.

ABSTRACT
Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS) in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients' 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7) and a human T-cell leukemia cell line (CCRF-CEM). PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P = 0.038; n = 193). Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.

No MeSH data available.


Related in: MedlinePlus