Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press2110.17650/1994-4098-2014-0-2-16-22MAMMOLOGY. TOPICAL ISSUEМАММОЛОГИЯ. АКТУАЛЬНАЯ ТЕМА5-PGDH expression in breast cancer cellsЭкспрессия 15-PGDH в клетках рака молочной железыTaipovM. A.ТаиповМ. А.
Russian Federation
taipoff.m@yandex.ruNikiforovaZ. N.НикифороваЗ. Н.
Russian Federation
PavlovaO. M.ПавловаО. М.
Russian Federation
KudryavtsevI. A.КудрявцевИ. А.
Russian Federation
ArnotskayaN. Ye.АрноцкаяН. Е.
Russian Federation
ShevchenkoV. Ye.ШевченкоВ. Е.
Russian Federation
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowФБГУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва17072014216221807201418072014https://ojrs.abvpress.ru/ojrs/article/view/21

This paper analyzes 15-PGDH gene expression in the human breast cancer (BC) cell liness and describes the molecular principles through which the expression of the enzyme 15-PGDH is controlled in the tumor cells with a varying metastatic potential. There is an inverse correla- tion of 15-PGDH gene expression with COX-2 expression and the metastatic potential of tumor cells. Investigation of mechanisms for 15-PGDH regulation opens up new vistas and possibilities for the design of effective drugs for the targeted therapy of metastatic forms of BC.

В данной работе проведен анализ экспрессии гена 15-PGDH в линиях клеток рака молочной железы (РМЖ) человека. В результа- те описаны молекулярные принципы, посредством которых в опухолевых клетках c разным потенциалом к метастазированию регулируется экспрессия фермента 15-PGDH. Выявлена обратная корреляция экспрессии гена 15-PGDH с экспрессией COX-2 и потенциалом опухолевых клеток к метастазированию. Исследование механизмов регуляции 15-PGDH открывает новые пути и возможности для создания эффективных препаратов направленной терапии для лечения метастатических форм РМЖ.

breast cancerCOX-1COX-215-PGDHpredictive marker for breast cancerCOX-2 inhibitorsPGE2MCF-7BT-474and ZR-75-1 human breast tumor cell linestargeted therapy goalрак молочной железыCOX-1COX-215-PGDHпрогностический маркер рака молочной железыингибиторы COX-2PGE2линии опухолевых клеток молочной железы человека MCF-7BT-474ZR-75-1мишень для направленной терапии1. Аксель Е.М., Давыдов М.И. Заболеваемость злокачественными новообразованиями населения России и стран СНГ в 2008 г. Вестн РОНЦ 2010;21(2 прил 1):52–86.Аксель Е.М., Давыдов М.И. Заболеваемость злокачественными новообразованиями населения России и стран СНГ в 2008 г. Вестн РОНЦ 2010;21(2 прил 1):52–86.2. Greenlee R.T., Murray T., Bolden S., Wingo P.A. Cancer statistics, 2000. CA Cancer J Clin 2000;50(1):7–33.Greenlee R.T., Murray T., Bolden S., Wingo P.A. Cancer statistics, 2000. CA Cancer J Clin 2000;50(1):7–33.3. Lin F., Luo J., Gao W. et al. COX-2 pro- motes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness. Tumour Biol 2013;34(5):2817–26.Lin F., Luo J., Gao W. et al. COX-2 pro- motes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness. Tumour Biol 2013;34(5):2817–26.4. Wolf I., O'Kelly J., Rubinek T. et al. 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res 2006;66(15):7818–23.Wolf I., O'Kelly J., Rubinek T. et al. 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res 2006;66(15):7818–23.5. Zhang B., Ma X., Li Z. et al. Celecoxib en- hances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating murine breast cancer. J Cancer Res Clin Oncol 2013;139(5):797–807.Zhang B., Ma X., Li Z. et al. Celecoxib en- hances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating murine breast cancer. J Cancer Res Clin Oncol 2013;139(5):797–807.6. Lehtinen L., Vainio P., Wikman H. et al. 15-Hydroxyprostaglandin dehydrogenase as- sociates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. J Pathol 2012;226(4):674–86.Lehtinen L., Vainio P., Wikman H. et al. 15-Hydroxyprostaglandin dehydrogenase as- sociates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. J Pathol 2012;226(4):674–86.7. Johnson R.F., Mitchell C.M., Clifton V., Zakar T. Regulation of 15-hydroxyprostaglan- din dehydrogenase (PGDH) gene activity, messenger ribonucleic acid processing, and protein abundance in the human chorionJohnson R.F., Mitchell C.M., Clifton V., Zakar T. Regulation of 15-hydroxyprostaglan- din dehydrogenase (PGDH) gene activity, messenger ribonucleic acid processing, and protein abundance in the human chorionin late gestation and labor. J Clin Endocrinol Metab 2004;89(11):5639–48.8. Bai J.W., Wang Z., Gui S.B., Zhang Y.Z. Loss of 15-hydroxyprostaglandin dehydroge- nase indicates a tumor suppressor role in pitu- itary adenomas. Oncol Rep 2012;28(2):714–20.Bai J.W., Wang Z., Gui S.B., Zhang Y.Z. Loss of 15-hydroxyprostaglandin dehydroge- nase indicates a tumor suppressor role in pitu- itary adenomas. Oncol Rep 2012;28(2):714–20.9. Miyoshi J., Yajima T., Shimamura K. et al. 5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumori- genesis. Anticancer Res 2012;32(4):1193–202. 10. Gonzalez-Villasana V., Gutiérrez-Puente Y., Tari A.M. Cyclooxygenase-2 utilizes Jun N- terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells. Oncol Rep 2013;30(3):1506–10.Miyoshi J., Yajima T., Shimamura K. et al. 5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumori- genesis. Anticancer Res 2012;32(4):1193–202. 10. Gonzalez-Villasana V., Gutiérrez-Puente Y., Tari A.M. Cyclooxygenase-2 utilizes Jun N- terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells. Oncol Rep 2013;30(3):1506–10.11. Ashok V., Dash C., Rohan T.E. et al. Selec- tive cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast 2011;20(1):66–70. 12. Cho M.H., Yoon J.H., Jaegal Y.J. et al. Ex- pression of cyclooxygenase-2 in breast carcino- genesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcino- ma. Breast 2006;15(3):390–8.Ashok V., Dash C., Rohan T.E. et al. Selec- tive cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast 2011;20(1):66–70. 12. Cho M.H., Yoon J.H., Jaegal Y.J. et al. Ex- pression of cyclooxygenase-2 in breast carcino- genesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcino- ma. Breast 2006;15(3):390–8.13. Choi D., Piao Y.L., Wu Y., Cho H. Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprosta- glandin dehydrogenase for wound healing. Bioorg Med Chem 2013;21(15):4477–84.Choi D., Piao Y.L., Wu Y., Cho H. Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprosta- glandin dehydrogenase for wound healing. Bioorg Med Chem 2013;21(15):4477–84.14. Lu D., Han C., Wu T. 15-hydroxyprosta- glandin dehydrogenase-derived 15-keto-prosta- glandin E2 Inhibits cholangiocarcinoma cell growth through interaction with peroxisome proliferator-activated receptor- , SMAD2/3, and TAP63 proteins. J Biol Chem 2013;288(27):19484–502.Lu D., Han C., Wu T. 15-hydroxyprosta- glandin dehydrogenase-derived 15-keto-prosta- glandin E2 Inhibits cholangiocarcinoma cell growth through interaction with peroxisome proliferator-activated receptor- , SMAD2/3, and TAP63 proteins. J Biol Chem 2013;288(27):19484–502.15. Wakimoto N., Wolf I., Yin D. et al. Nonsteroidal anti-inflammatory drugs suppress glioma via 15-hydroxyprostaglandin dehydrogenase. Cancer Res 2008;68(17): 6978–86.Wakimoto N., Wolf I., Yin D. et al. Nonsteroidal anti-inflammatory drugs suppress glioma via 15-hydroxyprostaglandin dehydrogenase. Cancer Res 2008;68(17): 6978–86.16. Subbaramaiah K., Howe L.R., Zhou X.K. et al. Pioglitazone, a PPAR agonist, suppresses CYP19 transcription: evidence for involvement of 15-hydroxyprostaglandin dehydrogenase and BRCA1. Cancer Prev Res (Phila) 2012;5(10):1183–94.Subbaramaiah K., Howe L.R., Zhou X.K. et al. Pioglitazone, a PPAR agonist, suppresses CYP19 transcription: evidence for involvement of 15-hydroxyprostaglandin dehydrogenase and BRCA1. Cancer Prev Res (Phila) 2012;5(10):1183–94.17. Zhang B., Ma X., Li Z. et al. Celecoxib en- hances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating murine breast cancer. J Cancer Res Clin Oncol 2013;139(5):797–807.Zhang B., Ma X., Li Z. et al. Celecoxib en- hances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating murine breast cancer. J Cancer Res Clin Oncol 2013;139(5):797–807.18. Lou L.H., Jing D.D., Lai Y.X. et al. 15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma. World J Gastroenterol 2012;18(10):1028–37. 19. Wolf I., O'Kelly J., Rubinek T. et al. 15 hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res 2006;66(15):7818–23.Lou L.H., Jing D.D., Lai Y.X. et al. 15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma. World J Gastroenterol 2012;18(10):1028–37. 19. Wolf I., O'Kelly J., Rubinek T. et al. 15 hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res 2006;66(15):7818–23.20. Na H.K., Park J.M., Lee H.G. et al. 15-Hydroxyprostaglandin dehydrogenase as a novel molecular target for cancer chemoprevention and therapy. Biochem Pharmacol 2011;82(10):1352–60.Na H.K., Park J.M., Lee H.G. et al. 15-Hydroxyprostaglandin dehydrogenase as a novel molecular target for cancer chemoprevention and therapy. Biochem Pharmacol 2011;82(10):1352–60.21. Roberts H.R., Smartt H.J., Greenhough A. et al. Colon tumour cells increase PGE(2) by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation. Carcinogenesis 2011;32(11):1741–7.Roberts H.R., Smartt H.J., Greenhough A. et al. Colon tumour cells increase PGE(2) by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation. Carcinogenesis 2011;32(11):1741–7.22. Thill M., Fischer D., Kelling K. et al. Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients.Thill M., Fischer D., Kelling K. et al. Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients.J Steroid Biochem Mol Biol 2010; 121(1–2):387–90.23. Moore A.E., Greenhough A., Roberts H.R. et al. HGF/Met signalling promotes PGE(2) biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells. Carcinogenesis 2009;30(10):1796–804.Moore A.E., Greenhough A., Roberts H.R. et al. HGF/Met signalling promotes PGE(2) biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells. Carcinogenesis 2009;30(10):1796–804.24. Cordes T., Hoellen F., Dittmer C. et al. Correlation of prostaglandin metabolizing enzymes and serum PGE2 levels with vitamin D receptor and serum 25(OH)2D3 levels in breast and ovarian cancer. Anticancer Res 2012;32(1): 351–7.Cordes T., Hoellen F., Dittmer C. et al. Correlation of prostaglandin metabolizing enzymes and serum PGE2 levels with vitamin D receptor and serum 25(OH)2D3 levels in breast and ovarian cancer. Anticancer Res 2012;32(1): 351–7.25. Lehtinen L., Vainio P., Wikman H. et al. 15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. J Pathol 2012;226(4):Lehtinen L., Vainio P., Wikman H. et al. 15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. J Pathol 2012;226(4):674–86.–86.