THE ASSOCIATION OF PROTEASOME ACTIVITY AND SUBUNITS COMPOSITION WITH ESTROGEN AND PROGESTERONE RECEPTORS EXPRESSION IN BREAST АND ENDOMETRIAL CANCERS

Е.Е. Shashova (1), L.V. Spirina (1), I.V. Kondakova (1), E.M. Slonimskaya (1,2), L.A. Kolomiets (1,2), A.L. Chernyshova (1), S.A. Glushchenko (1), O.V. Savenkova (1)
1 -Tomsk Cancer Research Institute of RAMS, Russian Federation, 634050, Tomsk, Kooperativnaya Str., 5;
2 -Siberian State Medical University, Russian Federation, 634050, Tomsk Moscowsky Trakt, 2

Introduction. The features of pathogenesis of main tumors of the female reproductive system are determined by the impact of estrogen on target tissues. In this connection there appears the need to study the regulation of estrogen and progesterone receptors in the tumor tissues of breast and endometrium. The aim of the study. To investigate the association of proteasomes activity and subunit composition of with receptor status of breast and endometrial cancer. Methods. The study included 74 patients with operable breast cancer T1-4N0-3M0 not receiving neoadjuvant treatment, and 27 ER patients at the stage I-II. The total proteasome activity was determined according to hydrolysis of the fluorogenic oligopeptide Suc-LLVY- AMC and under the action of the inhibitor MG132. The separation of proteasomes into pools was performed with the method of fractionation the the use of ammonium sulfate. Proteasome subunit composition was investigated with the aid of Western blot method.Results. Breast tumors were shown to be characterized by a significant change in proteasome subunit composition in dependence on the severity of the expression of estrogen receptors. In breast cancer the content of almost all subunits was higher in smaller expression index of estrogen receptors. Endometrial cancer was characterized by marked change in activity of 26S proteasome pool in dependence on the expression of estrogen receptors. Also, in ER there are observed significant changes in the level of α1α2α3α5α6α7 subunit in dependence on the extent of expression of progesterone receptors. Conclusion. The obtained results indicate to the need for further study of proteasome system in comparison with the expression of the female sex steroid hormones. It is necessary to assess in what extent the association of proteasome system with the expression of estrogen receptors and progesterone is functional and how it can be linked with the outcome of breast cancer and endometrial cancer.
Keywords: 
breast cancer, endometrial cancer, estrogen and progesterone receptors, proteasome