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mPGES-1 in prostate cancer controls stemness and amplifies epidermal growth factor receptor-driven oncogenicity.

Finetti F, Terzuoli E, Giachetti A, Santi R, Villari D, Hanaka H, Radmark O, Ziche M, Donnini S - Endocr. Relat. Cancer (2015)

Bottom Line: There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood.They also show increased capacity to survive irrespective of anchorage condition, and overexpress EGFR compared to mPGES-1(KD) cells. mPGES-1 expression correlates with increased in vivo tumour growth and metastasis.Although EGFR inhibition reduces mPGES-1(SC) and mPGES-1(KD) cell xenograft tumour growth, we show that mPGES-1/PGE2 signalling sensitizes tumour cells to EGFR inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Department of Life SciencesUniversity of Siena, Via Aldo Moro 2, 53100 Siena, ItalyDepartment of Surgery and Translational MedicineUniversity of Florence, Largo Brambilla 3, 50134 Firenze, ItalyDepartment of Clinical and Experimental MedicineUniversity of Florence, Viale Pieraccini 18, 50139 Firenze, ItalyDepartment of Medical Biochemistry and BiophysicsKarolinska Institutet, SE-171 77 Stockholm, SwedenIstituto Toscano Tumori (ITT)Firenze, Italy.

No MeSH data available.


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mPGES-1 promotes EMT in DU145 cells. (A) Expression of enzymes involved in arachidonic acid cascade in DU145 WT, mPGES-1SC and mPGES-1KD cell lines in basal condition (10% FCS) measured by western blot. (B) EIA analysis of PGE2 production measured in medium conditioned by DU145 cells. Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. ***P<0.001 vs mPGES-1SC-. (C and D) Representative images and quantification of western blot analysis of E-cadherin, vimentin, fibronectin and ahnak expression in DU145 cells. *P<0.05, **P<0.01 and ***P<0.001 vs DU145 mPGES-1SC (E) Western blot analysis of fibronectin and vimentin in mPGES-1KD cells treated with PGE2 (1 μmol/l, 24 h). (F) Western blot analysis of β-catenin localization in DU145 mPGES-1SC and mPGES-1KD cells. Nuc, nucleus; Cyt, cytoplasm.
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fig2: mPGES-1 promotes EMT in DU145 cells. (A) Expression of enzymes involved in arachidonic acid cascade in DU145 WT, mPGES-1SC and mPGES-1KD cell lines in basal condition (10% FCS) measured by western blot. (B) EIA analysis of PGE2 production measured in medium conditioned by DU145 cells. Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. ***P<0.001 vs mPGES-1SC-. (C and D) Representative images and quantification of western blot analysis of E-cadherin, vimentin, fibronectin and ahnak expression in DU145 cells. *P<0.05, **P<0.01 and ***P<0.001 vs DU145 mPGES-1SC (E) Western blot analysis of fibronectin and vimentin in mPGES-1KD cells treated with PGE2 (1 μmol/l, 24 h). (F) Western blot analysis of β-catenin localization in DU145 mPGES-1SC and mPGES-1KD cells. Nuc, nucleus; Cyt, cytoplasm.

Mentions: In DU145 cell line isolated from a castration-resistant human brain metastasis of PCa, characterized by mPGES-1 expression (mPGES-1SC) (Hanaka et al. 2009), the knock down for mPGES-1 (stable or transient mPGES-1KD) did not affect PGE2 receptor expression (EP1-4), while it obliterated PGE2 output (>90%, P<0.001 vs mPGES-1SC) (A and B, and Supplementary Figure 1, see section on supplementary data given at the end of this article). The large PGE2 loss occurred despite a slight increase in cyclooxygenase-2 (COX-2) expression, while other enzymes involved in PGE2 metabolism were either unchanged (e.g. COX-1), or only negligibly changed (e.g. the cytosolic isoform, cPGES, the microsomal type 2 isoform, mPGES-2, the prostaglandin transporter, PGT and the enzyme implicated in PGE2 degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH)) (Fig. 2A). Compared to DU145 WT, transfection of cells with the empty vector (mPGES-1SC) did not affect the PGE2 signalling cascade (Fig. 2A). Similar results were obtained in experiments of transiently silenced mPGES-1 cells (Supplementary Figure 2A).


mPGES-1 in prostate cancer controls stemness and amplifies epidermal growth factor receptor-driven oncogenicity.

Finetti F, Terzuoli E, Giachetti A, Santi R, Villari D, Hanaka H, Radmark O, Ziche M, Donnini S - Endocr. Relat. Cancer (2015)

mPGES-1 promotes EMT in DU145 cells. (A) Expression of enzymes involved in arachidonic acid cascade in DU145 WT, mPGES-1SC and mPGES-1KD cell lines in basal condition (10% FCS) measured by western blot. (B) EIA analysis of PGE2 production measured in medium conditioned by DU145 cells. Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. ***P<0.001 vs mPGES-1SC-. (C and D) Representative images and quantification of western blot analysis of E-cadherin, vimentin, fibronectin and ahnak expression in DU145 cells. *P<0.05, **P<0.01 and ***P<0.001 vs DU145 mPGES-1SC (E) Western blot analysis of fibronectin and vimentin in mPGES-1KD cells treated with PGE2 (1 μmol/l, 24 h). (F) Western blot analysis of β-catenin localization in DU145 mPGES-1SC and mPGES-1KD cells. Nuc, nucleus; Cyt, cytoplasm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4526795&req=5

fig2: mPGES-1 promotes EMT in DU145 cells. (A) Expression of enzymes involved in arachidonic acid cascade in DU145 WT, mPGES-1SC and mPGES-1KD cell lines in basal condition (10% FCS) measured by western blot. (B) EIA analysis of PGE2 production measured in medium conditioned by DU145 cells. Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. ***P<0.001 vs mPGES-1SC-. (C and D) Representative images and quantification of western blot analysis of E-cadherin, vimentin, fibronectin and ahnak expression in DU145 cells. *P<0.05, **P<0.01 and ***P<0.001 vs DU145 mPGES-1SC (E) Western blot analysis of fibronectin and vimentin in mPGES-1KD cells treated with PGE2 (1 μmol/l, 24 h). (F) Western blot analysis of β-catenin localization in DU145 mPGES-1SC and mPGES-1KD cells. Nuc, nucleus; Cyt, cytoplasm.
Mentions: In DU145 cell line isolated from a castration-resistant human brain metastasis of PCa, characterized by mPGES-1 expression (mPGES-1SC) (Hanaka et al. 2009), the knock down for mPGES-1 (stable or transient mPGES-1KD) did not affect PGE2 receptor expression (EP1-4), while it obliterated PGE2 output (>90%, P<0.001 vs mPGES-1SC) (A and B, and Supplementary Figure 1, see section on supplementary data given at the end of this article). The large PGE2 loss occurred despite a slight increase in cyclooxygenase-2 (COX-2) expression, while other enzymes involved in PGE2 metabolism were either unchanged (e.g. COX-1), or only negligibly changed (e.g. the cytosolic isoform, cPGES, the microsomal type 2 isoform, mPGES-2, the prostaglandin transporter, PGT and the enzyme implicated in PGE2 degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH)) (Fig. 2A). Compared to DU145 WT, transfection of cells with the empty vector (mPGES-1SC) did not affect the PGE2 signalling cascade (Fig. 2A). Similar results were obtained in experiments of transiently silenced mPGES-1 cells (Supplementary Figure 2A).

Bottom Line: There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood.They also show increased capacity to survive irrespective of anchorage condition, and overexpress EGFR compared to mPGES-1(KD) cells. mPGES-1 expression correlates with increased in vivo tumour growth and metastasis.Although EGFR inhibition reduces mPGES-1(SC) and mPGES-1(KD) cell xenograft tumour growth, we show that mPGES-1/PGE2 signalling sensitizes tumour cells to EGFR inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Department of Life SciencesUniversity of Siena, Via Aldo Moro 2, 53100 Siena, ItalyDepartment of Surgery and Translational MedicineUniversity of Florence, Largo Brambilla 3, 50134 Firenze, ItalyDepartment of Clinical and Experimental MedicineUniversity of Florence, Viale Pieraccini 18, 50139 Firenze, ItalyDepartment of Medical Biochemistry and BiophysicsKarolinska Institutet, SE-171 77 Stockholm, SwedenIstituto Toscano Tumori (ITT)Firenze, Italy.

No MeSH data available.


Related in: MedlinePlus