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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.


Related in: MedlinePlus

Pharmacological inhibition of mPGES-1 controls EMT markers, α6-integrin and EGFR expression, and reduces prostate cancer cells growth. (A). EIA analysis of PGE2 production measured in medium conditioned by DU145 or PC-3 cells after 48 h of treatment with MF63 (10 μmol/l). Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. **P<0.01 vs basal. (B, C and D) Western blot analysis of E-cadherin, vimentin and α6-integrin expression after MF63 treatment (10 μmol/l). (E). Quantification of DU145 and PC-3 colonies in the presence or absence of MF-63 10 μmol/l. Data are reported as the number of colonies of three experiments in triplicate. *P<0.05 and **P<0.01 vs basal PC-3; #P<0.05 and ###P<0.001 vs basal DU145.
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fig4: Pharmacological inhibition of mPGES-1 controls EMT markers, α6-integrin and EGFR expression, and reduces prostate cancer cells growth. (A). EIA analysis of PGE2 production measured in medium conditioned by DU145 or PC-3 cells after 48 h of treatment with MF63 (10 μmol/l). Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. **P<0.01 vs basal. (B, C and D) Western blot analysis of E-cadherin, vimentin and α6-integrin expression after MF63 treatment (10 μmol/l). (E). Quantification of DU145 and PC-3 colonies in the presence or absence of MF-63 10 μmol/l. Data are reported as the number of colonies of three experiments in triplicate. *P<0.05 and **P<0.01 vs basal PC-3; #P<0.05 and ###P<0.001 vs basal DU145.

Mentions: Further evidence that the mPGES-1-PGE2 cascade enhances PCa cell aggressiveness was obtained by inhibiting mPGES-1 activity with the selective inhibitor MF63 (Xu et al. 2008). MF63 (10 μmol/l, 24–48 h) significantly inhibited PGE2 production and reversed the mesenchymal phenotype in DU145 and PC-3 cells, promoting E-cadherin and inhibiting vimentin expression (Fig. 4A, B and C). MF63 also upregulated α6-integrin and significantly reduced cell clonogenicity (Fig. 4D and E).


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)

Pharmacological inhibition of mPGES-1 controls EMT markers, α6-integrin and EGFR expression, and reduces prostate cancer cells growth. (A). EIA analysis of PGE2 production measured in medium conditioned by DU145 or PC-3 cells after 48 h of treatment with MF63 (10 μmol/l). Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. **P<0.01 vs basal. (B, C and D) Western blot analysis of E-cadherin, vimentin and α6-integrin expression after MF63 treatment (10 μmol/l). (E). Quantification of DU145 and PC-3 colonies in the presence or absence of MF-63 10 μmol/l. Data are reported as the number of colonies of three experiments in triplicate. *P<0.05 and **P<0.01 vs basal PC-3; #P<0.05 and ###P<0.001 vs basal DU145.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4526795&req=5

fig4: Pharmacological inhibition of mPGES-1 controls EMT markers, α6-integrin and EGFR expression, and reduces prostate cancer cells growth. (A). EIA analysis of PGE2 production measured in medium conditioned by DU145 or PC-3 cells after 48 h of treatment with MF63 (10 μmol/l). Results (three experiments run in duplicate) are expressed as pg/ml of PGE2. **P<0.01 vs basal. (B, C and D) Western blot analysis of E-cadherin, vimentin and α6-integrin expression after MF63 treatment (10 μmol/l). (E). Quantification of DU145 and PC-3 colonies in the presence or absence of MF-63 10 μmol/l. Data are reported as the number of colonies of three experiments in triplicate. *P<0.05 and **P<0.01 vs basal PC-3; #P<0.05 and ###P<0.001 vs basal DU145.
Mentions: Further evidence that the mPGES-1-PGE2 cascade enhances PCa cell aggressiveness was obtained by inhibiting mPGES-1 activity with the selective inhibitor MF63 (Xu et al. 2008). MF63 (10 μmol/l, 24–48 h) significantly inhibited PGE2 production and reversed the mesenchymal phenotype in DU145 and PC-3 cells, promoting E-cadherin and inhibiting vimentin expression (Fig. 4A, B and C). MF63 also upregulated α6-integrin and significantly reduced cell clonogenicity (Fig. 4D and E).

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