oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciencesoncotomsk-9Research ArticleОБЗОРЫREVIEWSРЕЦЕПТОРЫ РОСТОВЫХ ФАКТОРОВ И АДИПОКИНОВ В ПАТОГЕНЕЗЕ И ПРОГНОЗЕ РАКА ЭНДОМЕТРИЯ НА ФОНЕ МЕТАБОЛИЧЕСКОГО СИНДРОМАGROWTH FACTOR AND ADIPOKINE RECEPTORS IN PATHOGENESIS AND PROGNOSIS OF ENDOMETRIAL CANCER IN PATIENTS WITH METABOLIC SYNDROMEЮнусоваН. В.YunusovaN. V.bochkarevanv@oncology.tomsk.ruКондаковаИ. В.KondakovaI. V.bochkarevanv@oncology.tomsk.ruКоломиецЛ. А.KolomietsL. А.

634050, г. Томск, пер. Кооперативный, 5

5, Kooperativny Street, 63405-Tomsk

bochkarevanv@oncology.tomsk.ruЧернышоваА. Л.ChernyshovaА. L.bochkarevanv@oncology.tomsk.ruШаншашвилиЕ. В.ShanshashviliЕ. V.bochkarevanv@oncology.tomsk.ruФГБУ «НИИ онкологии» СО РАМН, г. ТомскРоссияCancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, TomskRussian FederationФГБУ «НИИ онкологии» СО РАМН, г. Томск Сибирский государственный медицинский университет, г. ТомскРоссияCancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk Siberian State Medical University, TomskRussian Federation201405022016014145Copyright © Юнусова Н.В., Кондакова И.В., Коломиец Л.А., Чернышова А.Л., Шаншашвили Е.В., 20162016Юнусова Н.В., Кондакова И.В., Коломиец Л.А., Чернышова А.Л., Шаншашвили Е.В.Yunusova N.V., Kondakova I.V., Kolomiets L.А., Chernyshova А.L., Shanshashvili Е.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/9

В обзоре обсуждается роль рецепторов ростовых факторов (инсулиноподобного фактора роста и трансформирующего фактора роста beta) и адипокинов (лептина и адипонектина) в патогенезе рака эндометрия на фоне метаболического синдрома. Нижележащим эффектором активируемых ростовыми факторами и данными цитокинами сигнальных путей является циклооксигеназа-2. Представляется весьма перспективным изучение более детальных механизмов вовлеченности этих протеинов в патогенез рака эндометрия на фоне метаболического синдрома с поиском новых биологических прогностических биомаркеров у этой категории больных.

The role of growth factor receptors (insulin-like growth factor and transforming growth factor-beta) and adipokine receptors (leptin and adiponectin) in pathogenesis of endometrial cancer under conditions of metabolic syndrome is discussed. Cyclooxygenase-2 is an effector of signaling pathways activated by growth factors and cytokines. The detailed study of the mechanisms involving these proteins in pathogenesis of endometrial cancer in patients with metabolic syndrome and search for new biological prognostic markers appear to be promising.

рецепторы ростовых фактороврецепторы адипокиновциклооксигеназа-2рак эндометрияметаболический синдромgrowth factor receptorsadipokine receptorscyclooxygenase-2endometrial cancermetabolic syndromeReferencesБерштейн Л.М. Онкоэндокринология: традиции, современность, перспективы. СПб.: Наука, 2004. 150 с.Берштейн Л.М. Онкоэндокринология: традиции, современность, перспективы. СПб.: Наука, 2004. 150 с.Болдарян Н.А., Пожарисский К.М., Винокуров В.Л. и др. Прогностическое значение уровня экспрессии циклооксигеназ (COX-1, COX-2) при раке эндометрия // Вопросы онкологии. 2008. Т. 54, № 1. C. 40–46.Болдарян Н.А., Пожарисский К.М., Винокуров В.Л. и др. Прогностическое значение уровня экспрессии циклооксигеназ (COX-1, COX-2) при раке эндометрия // Вопросы онкологии. 2008. Т. 54, № 1. C. 40–46.Бочкарева Н.В., Кондакова И.В., Коломиец Л.А. и др. Инсулиноподобные факторы роста в патогенезе и прогнозе рака яичников // Сибирский онкологический журнал. 2011. № 3 (45). С. 74–81.Бочкарева Н.В., Кондакова И.В., Коломиец Л.А. и др. Инсулиноподобные факторы роста в патогенезе и прогнозе рака яичников // Сибирский онкологический журнал. 2011. № 3 (45). С. 74–81.Коломиец Л.А., Бочкарева Н.В., Чернышова А.Л. Рак эндометрия и метаболический синдром. Томск: Иван Федоров, 2010. 228 c.Коломиец Л.А., Бочкарева Н.В., Чернышова А.Л. Рак эндометрия и метаболический синдром. Томск: Иван Федоров, 2010. 228 c.Копнин Б.П. Компоненты сигнальных путей TGFβ-Smad // Канцерогенез / под ред. Д.Г. Заридзе. М.: Медицина, 2004. С. 147–148.Копнин Б.П. Компоненты сигнальных путей TGFβ-Smad // Канцерогенез / под ред. Д.Г. Заридзе. М.: Медицина, 2004. С. 147–148.Спирина Л.В., Бочкарева Н.В., Кондакова И.В. и др. Регуляция инсулиноподобных факторов роста и NF-kappaB протеасомной системой при раке эндометрия // Мол. биология. 2012. Т. 46, № 3. C. 453–460.Спирина Л.В., Бочкарева Н.В., Кондакова И.В. и др. Регуляция инсулиноподобных факторов роста и NF-kappaB протеасомной системой при раке эндометрия // Мол. биология. 2012. Т. 46, № 3. C. 453–460.Antunes A.J., Andrade L.A., Pinto G.A. et al. Is the immunohistochemical expression of proliferation (Ki-67) and apoptosis (Bcl-2) markers and cyclooxigenase-2 (COX-2) related to carcinogenesis in postmenopausal endometrial polyps? // Anal. Quant. Cytol. Histol. 2012. Vol. 34 (5). P. 264–272.Antunes A.J., Andrade L.A., Pinto G.A. et al. Is the immunohistochemical expression of proliferation (Ki-67) and apoptosis (Bcl-2) markers and cyclooxigenase-2 (COX-2) related to carcinogenesis in postmenopausal endometrial polyps? // Anal. Quant. Cytol. Histol. 2012. Vol. 34 (5). P. 264–272.Asiedu M. K., Ingle J.N., Behrens M.D. et al. TGFβ/TNFα-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype // Cancer Res. 2011. Vol. 71 (13). P. 4707–4719.Asiedu M. K., Ingle J.N., Behrens M.D. et al. TGFβ/TNFα-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype // Cancer Res. 2011. Vol. 71 (13). P. 4707–4719.Caja L., Sancho P., Bertran E. et al. Overactivation of the MEK/ ERK pathway in liver tumor cells confer resistance to TGF-beta –induced cell death througf impairing up-regulation of the NADH oxidase NOX4 // Cancer Res. 2009. Vol. 69 (19). P. 7595–7602.Caja L., Sancho P., Bertran E. et al. Overactivation of the MEK/ ERK pathway in liver tumor cells confer resistance to TGF-beta –induced cell death througf impairing up-regulation of the NADH oxidase NOX4 // Cancer Res. 2009. Vol. 69 (19). P. 7595–7602.Esposito K., Chiodini P., Colao A. et al. Metabolic syndrome and risk of cancer. A systematic review and meta-analysis // Diabetes Care. 2012. Vol. 35. P. 2402–2411.Esposito K., Chiodini P., Colao A. et al. Metabolic syndrome and risk of cancer. A systematic review and meta-analysis // Diabetes Care. 2012. Vol. 35. P. 2402–2411.Firth S.M., Baxter R.C. Cellular action of the insuline-like growth factor binding proteins // Endocrine reviews. 2002. Vol. 23 (6). P. 824–854.Firth S.M., Baxter R.C. Cellular action of the insuline-like growth factor binding proteins // Endocrine reviews. 2002. Vol. 23 (6). P. 824–854.Gao J., Tian J., Lu Y. et al. Leptin induced functional activation of cyclooxygenase-2 throuth JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells // Cancer Sci. 2009. Vol. 100 (3). P. 389–395.Gao J., Tian J., Lu Y. et al. Leptin induced functional activation of cyclooxygenase-2 throuth JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells // Cancer Sci. 2009. Vol. 100 (3). P. 389–395.Gorska E., Popko K., Stelmaszczyk-Emmel A. et al. Leptin receptors // Eur. J. Med. Res. 2010. Vol. 15. Suppl. 2. P. 50–54.Gorska E., Popko K., Stelmaszczyk-Emmel A. et al. Leptin receptors // Eur. J. Med. Res. 2010. Vol. 15. Suppl. 2. P. 50–54.Jongen V.H., Briet J.M., de Jong R.A. et al. Aromatase, cyclooxygenase-2, HER-2/neu and p53 as prognostic factors in endometrioid endometrial cancer // Int. J. Gynecol. Cancer. 2009. Vol. 19 (4). P. 670–676.Jongen V.H., Briet J.M., de Jong R.A. et al. Aromatase, cyclooxygenase-2, HER-2/neu and p53 as prognostic factors in endometrioid endometrial cancer // Int. J. Gynecol. Cancer. 2009. Vol. 19 (4). P. 670–676.Kesser S.H., Gul A.E., Barisik N.O. et al. The relationship of COX-2 expression with estrogen receptor, progesterone receptor and prognostic parameters in endometrial carcinomas // J. Obstet. Gynaecol. Res. 2010. Vol. 36 (3). P. 560–566.Kesser S.H., Gul A.E., Barisik N.O. et al. The relationship of COX-2 expression with estrogen receptor, progesterone receptor and prognostic parameters in endometrial carcinomas // J. Obstet. Gynaecol. Res. 2010. Vol. 36 (3). P. 560–566.Koda M., Sulkowska M., Wincewicz A. et al. Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer // Ann. N.Y. Acad. Sci. 2007. Vol. 1095. P. 90–98.Koda M., Sulkowska M., Wincewicz A. et al. Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer // Ann. N.Y. Acad. Sci. 2007. Vol. 1095. P. 90–98.Mantzos F., Vanakara P., Samara S. et al. Leptin receptor expression in neoplastic and normal ovarian and endometrial tissue // Eur. J. Gynaecol. Oncol. 2011. Vol. 32 (1). P. 84–86.Mantzos F., Vanakara P., Samara S. et al. Leptin receptor expression in neoplastic and normal ovarian and endometrial tissue // Eur. J. Gynaecol. Oncol. 2011. Vol. 32 (1). P. 84–86.McCambell A.S., Broaddus R.R., Loose D.S. et al. Overexpression of the insuline-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium // Clin. Cancer Res. 2006. Vol. 12. P. 6373–6378.McCambell A.S., Broaddus R.R., Loose D.S. et al. Overexpression of the insuline-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium // Clin. Cancer Res. 2006. Vol. 12. P. 6373–6378.Moon H.S., Shamberland J.P., Aronis K. et al. Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans // Mol. Cancer Ther. 2011. Vol. 10 (12). P. 2234–2243.Moon H.S., Shamberland J.P., Aronis K. et al. Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans // Mol. Cancer Ther. 2011. Vol. 10 (12). P. 2234–2243.Pennisi A.P., Barr V., Nunez N.P. et al. Reduced expression of insuline-like growth factor I receptors in MCF breast cancer cells leads to a more metastatic phenotype // Cancer Res. 2002. Vol. 62. P. 6529–6537.Pennisi A.P., Barr V., Nunez N.P. et al. Reduced expression of insuline-like growth factor I receptors in MCF breast cancer cells leads to a more metastatic phenotype // Cancer Res. 2002. Vol. 62. P. 6529–6537.Piestrzeniewicz-Ulanska D., Brys M., Semczuk A. et al. TGF-beta signaling is disrupted in endometrial-type endometrial carcinomas // Gynecol. Oncol. 2004. Vol. 95 (1). P. 173–180.Piestrzeniewicz-Ulanska D., Brys M., Semczuk A. et al. TGF-beta signaling is disrupted in endometrial-type endometrial carcinomas // Gynecol. Oncol. 2004. Vol. 95 (1). P. 173–180.Rosato V., Zucchetto A., Bosetti C. et al. Metabolic syndrome and endometrial cancer risk // Ann. Oncol. 2011. Vol. 22. P. 882–889.Rosato V., Zucchetto A., Bosetti C. et al. Metabolic syndrome and endometrial cancer risk // Ann. Oncol. 2011. Vol. 22. P. 882–889.Schaab M., Kausch H., Klammt J. et al. Novel regulatory mechanism for generation of the soluble leotin receptor: implications for leptin action // PLoS One. 2012. Vol. 7 (4). E. 34787.Schaab M., Kausch H., Klammt J. et al. Novel regulatory mechanism for generation of the soluble leotin receptor: implications for leptin action // PLoS One. 2012. Vol. 7 (4). E. 34787.Sharma D., Saxena N.K., Vertino P.M et al. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways // Endocr. Relat. Cancer. 2006. Vol. 13 (2). P. 629–640.Sharma D., Saxena N.K., Vertino P.M et al. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways // Endocr. Relat. Cancer. 2006. Vol. 13 (2). P. 629–640.Seeber L. M., Zweemer R.P., Verheijen R.H. et al. Hypoxia-inducible factor-1 as a therapeutic target in endometrial cancer management // Obstet. Gynecol. Int. 2010; 2010: 580971. doi: 10.1155/2010/580971.Seeber L. M., Zweemer R.P., Verheijen R.H. et al. Hypoxia-inducible factor-1 as a therapeutic target in endometrial cancer management // Obstet. Gynecol. Int. 2010; 2010: 580971. doi: 10.1155/2010/580971.Steinbakk A., Gudlaugsson E., Aasprong O.Y. et al. Molecular biomarkers of endometrial hyperplasias predict cancer progression // Am. J. Obstset. Gynecol. 2011. Vol. 204 (4). P. 357. e. 1–12.Steinbakk A., Gudlaugsson E., Aasprong O.Y. et al. Molecular biomarkers of endometrial hyperplasias predict cancer progression // Am. J. Obstset. Gynecol. 2011. Vol. 204 (4). P. 357. e. 1–12.Wu X., Yan Q., Zhang Z. et al. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells // Oncol. Rep. 2012. Vol. 27 (5). P. 1488–1496.Wu X., Yan Q., Zhang Z. et al. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells // Oncol. Rep. 2012. Vol. 27 (5). P. 1488–1496.Yamauchi N., Takazawa Y., Maeda D. et al. Expression levels of adiponectin receptors are decreased in human endometrial adenocarcinoma tissues // Int. J. Gynecol. Pathol. 2012. Vol. 31 (4). P. 352–357.Yamauchi N., Takazawa Y., Maeda D. et al. Expression levels of adiponectin receptors are decreased in human endometrial adenocarcinoma tissues // Int. J. Gynecol. Pathol. 2012. Vol. 31 (4). P. 352–357.Yoneda K., Tomimoto A., Endo H. et al. Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue // Oncol. Rep. 2008. Vol. 20 (3). P. 479–483.Yoneda K., Tomimoto A., Endo H. et al. Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue // Oncol. Rep. 2008. Vol. 20 (3). P. 479–483.Zhou J-R., Blackburn G.L., Walker W.A. Symposium introduction: metabolic syndrome and the onset of cancer // Am. J. Clin. Nutr. 2007. Vol. 86 (3). P. 817S–819S.Zhou J-R., Blackburn G.L., Walker W.A. Symposium introduction: metabolic syndrome and the onset of cancer // Am. J. Clin. Nutr. 2007. Vol. 86 (3). P. 817S–819S.

The authors declare that there are no conflicts of interest present.