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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

mPGES-1 expression controls in vivo tumor growth, vimentin and EGFR expression. (A). Tumor volume measured in athymic mice inoculated with DU145 and PC-3 mPGES-1SC or mPGES-1KD cells after 12 or 21 days. *P<0.05 and **P<0.01 vs mPGES-1SC. (B) Immunohistochemical analysis of Ki67 expression in tumor specimens derived from mPGES-1SCor mPGES-1KD. Data are representative of five tumor specimens for both tumor cell types. (C and D) Western blot and immunohistochemical analysis of vimentin expression in xenograft tumor tissues. Data are representative of five tumor specimens for both tumor cell types. (E). Quantification and images of lung metastasis after injection in mice tail vein of DU145 or PC-3 mPGES-1SC or mPGES-1KD cells. Images: grey frame: DU145; black frame: PC-3. *P<0.05 and ##P<0.01 vs mPGES-1SC
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fig5: mPGES-1 expression controls in vivo tumor growth, vimentin and EGFR expression. (A). Tumor volume measured in athymic mice inoculated with DU145 and PC-3 mPGES-1SC or mPGES-1KD cells after 12 or 21 days. *P<0.05 and **P<0.01 vs mPGES-1SC. (B) Immunohistochemical analysis of Ki67 expression in tumor specimens derived from mPGES-1SCor mPGES-1KD. Data are representative of five tumor specimens for both tumor cell types. (C and D) Western blot and immunohistochemical analysis of vimentin expression in xenograft tumor tissues. Data are representative of five tumor specimens for both tumor cell types. (E). Quantification and images of lung metastasis after injection in mice tail vein of DU145 or PC-3 mPGES-1SC or mPGES-1KD cells. Images: grey frame: DU145; black frame: PC-3. *P<0.05 and ##P<0.01 vs mPGES-1SC

Mentions: In tumours induced by inoculating nude mice with mPGES-1SC or mPGES-1KD cells, the volume measurements (here reported at days 12 and 21) showed significant differences, growth being 2.3-fold higher in DU145 mPGES-1SC than mPGES-1KD tumours, and 4.9-fold higher in PC-3 mPGES-1SC than mPGES-1KD tumours (Fig. 5A). Consistently, Ki-67 showed denser immunostaining in mPGES-1SC than mPGES-1KD tumours (Fig. 5B). Accordingly, the Ki67 score was 45±2.9% and 57±3.8% for DU145 and PC-3 mPGES-1SC respectively and 21±1.9% and 29±1.8% for DU145 and PC-3 mPGES-1KD respectively, indicating a higher proliferation rate in cells overexpressing mPGES-1.


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 expression controls in vivo tumor growth, vimentin and EGFR expression. (A). Tumor volume measured in athymic mice inoculated with DU145 and PC-3 mPGES-1SC or mPGES-1KD cells after 12 or 21 days. *P<0.05 and **P<0.01 vs mPGES-1SC. (B) Immunohistochemical analysis of Ki67 expression in tumor specimens derived from mPGES-1SCor mPGES-1KD. Data are representative of five tumor specimens for both tumor cell types. (C and D) Western blot and immunohistochemical analysis of vimentin expression in xenograft tumor tissues. Data are representative of five tumor specimens for both tumor cell types. (E). Quantification and images of lung metastasis after injection in mice tail vein of DU145 or PC-3 mPGES-1SC or mPGES-1KD cells. Images: grey frame: DU145; black frame: PC-3. *P<0.05 and ##P<0.01 vs mPGES-1SC
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526795&req=5

fig5: mPGES-1 expression controls in vivo tumor growth, vimentin and EGFR expression. (A). Tumor volume measured in athymic mice inoculated with DU145 and PC-3 mPGES-1SC or mPGES-1KD cells after 12 or 21 days. *P<0.05 and **P<0.01 vs mPGES-1SC. (B) Immunohistochemical analysis of Ki67 expression in tumor specimens derived from mPGES-1SCor mPGES-1KD. Data are representative of five tumor specimens for both tumor cell types. (C and D) Western blot and immunohistochemical analysis of vimentin expression in xenograft tumor tissues. Data are representative of five tumor specimens for both tumor cell types. (E). Quantification and images of lung metastasis after injection in mice tail vein of DU145 or PC-3 mPGES-1SC or mPGES-1KD cells. Images: grey frame: DU145; black frame: PC-3. *P<0.05 and ##P<0.01 vs mPGES-1SC
Mentions: In tumours induced by inoculating nude mice with mPGES-1SC or mPGES-1KD cells, the volume measurements (here reported at days 12 and 21) showed significant differences, growth being 2.3-fold higher in DU145 mPGES-1SC than mPGES-1KD tumours, and 4.9-fold higher in PC-3 mPGES-1SC than mPGES-1KD tumours (Fig. 5A). Consistently, Ki-67 showed denser immunostaining in mPGES-1SC than mPGES-1KD tumours (Fig. 5B). Accordingly, the Ki67 score was 45±2.9% and 57±3.8% for DU145 and PC-3 mPGES-1SC respectively and 21±1.9% and 29±1.8% for DU145 and PC-3 mPGES-1KD respectively, indicating a higher proliferation rate in cells overexpressing mPGES-1.

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