ABERRANT TRANSCRIPTIONAL ACTIVITY OF APOPTOSIS-REGULATING GENES IN MALIGNANT NEOPLASM OF CORPUS UTERI

DOI: https://doi.org/10.29296/24999490-2018-01-05

O.I. Kit, D.I. Vodolazhsky, D.S. Kutilin, I.S. Nikitin, T.I. Moiseenko, E.M. Frantsiyants Rostov Research Institute of Oncology, 14 Line str., 63, Rostov-On-Don, Russian Federation, 344037 Е-mail: [email protected]

Introduction. The most common invasive malignant tumor of uterine is endometrial cancer. In process of tissues malignancy the critical role belongs to changes in signaling pathways which regulate apoptosis. The aim of study was to analyze changes in the expression of genes responsible for control of pro- and anti-apoptotic signaling cascades in endometrium cells. Methods. For studies of gene expression there were used tumor and conventionally normal tissues of corpus uteri from 27 patients. By RT-qPCR method there was explored the relative expression of 9 genetic loci: BAX, CASP7, CASP3, CASP8, CASP9, P53, C-FLIP, MDM2 and BCL2. Results. The expression of pro- and anti-apoptotic genetic loci at malignization endometrial tissue was found to possess characteristics associated with the age and degree of differentiation of neoplastic cell. This is reflected in the absence of significant changes in expression of investigated genes in patients under 55 years, in various transcriptional profile of these genes, which depended on the degree of the tumor grade, as well as violation of the transcriptional balance pairs of anti- and pro-apoptotic genes MDM2/P53 and BCL2/BAX, and their correlations with the decline in the level of cell differentiation (from G1 to G3). Conclusion. Detected changes in transcriptional balance of anti- and pro-apoptotic genes in malignancy uterine body tissues indicates to the violation of key mechanisms of the regulation of apoptosis, and can be used as an important diagnostic and prognostic parameters.
Keywords: 
corpus uteri cancer, apoptosis, gene expression, RT-PCR
Список литературы: 
  1. World Cancer Report 2014. International Agency for Research on Cancer. World Health Organization. 2014; 5: 12.
  2. Kaprin A.D, Starinskiy V.V., Petrova G.V. Zlokachestvennye novoobrazovaniya v Rossii v 2014 g. M.: MNIOI im. P.A. Gercena – filial FGBU «NMIRC» Minzdrava Rossii. 2016; 250
  3. [Kaprin A.D, Starinskij V.V., Petrova G.V. Zlokachestvennye novoobrazovanija v Rossii v 2014 godu. M.: MNIOI im. P.A. Gercena – filial FGBU «NMIRC» Minzdrava Rossii. 2016; 250 (in Russian)]
  4. Kit O.I., Vodolazhskiy D.I., Kutilin D.S., Nikitin I.S., Moiseenko T. I., Franciyanc E.M. Transkriptomnaya aktivnost` e`strogen-regulyatornyh genov pri malignizacii tkaney tela matki. Nauchnyy zhurnal KubGAU. 2016, 115(01): http://ej.kubagro.ru/2016/01/pdf/17.pdf
  5. [Kit O.I., Vodolazhskij D.I., Kutilin D.S., Nikitin I.S., Moiseenko T. I., Francijanc E.M. Transkriptomnaja aktivnost' jestrogen-reguljatornyh genov pri malignizacii tkanej tela matki. Nauchnyj zhurnal KubGAU. 2016, 115(01): http://ej.kubagro.ru/2016/01/pdf/17.pdf. (in Russian)]
  6. Kuramoto H., Nishida M. Cell and Molecular Biology of Endometrial Carcinoma. Springer Science & Business Media. 2012; 319.
  7. Vaskivuo T.E., Stenback F., Tapanainen J.S. Apoptosis and Apoptosis-Related Factors Bcl-2, Bax, Tumor Necrosis Factor-, and NF-B in Human Endometrial Hyperplasia and Carcinoma. Cancer. 2002; 95 (7): 1463–71.
  8. Kit O.I., Vodolazhskiy D.I., Kutilin D.S., Gudueva E.N. Izmenenie kopiynosti geneticheskih lokusov pri rake zheludka. Molekulyarnaya biologiya. 2015; 49 (4): 658–66.
  9. [Kit O.I., Vodolazhskij D.I., Kutilin D.S., Gudueva E.N. Izmenenie kopijnosti geneticheskih lokusov pri rake zheludka. Molekuljarnaja biologija. 2015; 49 (4): 658–66 (in Russian)]
  10. Kit O.I., Vodolazhskiy D.I., Kutilin D.S., Maleyko M.L., Dvadnenko K.V., Enin Ya.S., Gudueva E.N., Il`chenko S.A. Otnositel`naya kopiynost` apoptoz-reguliruyushhih genov kak pokazatel` malignizacii tkaney zheludka. Uspehi sovremennogo estestvoznaniya. 2015; 3: 40–5.
  11. [Kit O.I., Vodolazhskij D.I., Kutilin D.S., Malejko M.L., Dvadnenko K.V., Enin Ja.S., Gudueva E.N., Il'chenko S.A. Otnositel'naja kopijnost' apoptoz-regulirujushhih genov kak pokazatel' malignizacii tkanej zheludka. Uspehi sovremennogo estestvoznanija. 2015; 3: 40–5 (in Russian)]
  12. Kit O.I., Vodolazhskiy D.I. Molekulyarnaya biologiya kolorektal`nogo raka v klinicheskoy praktike. Molekulyarnaya biologiya. 2015; 49 (4): 531–40.
  13. [Kit O.I., Vodolazhskij D.I. Molekuljarnaja biologija kolorektal'nogo raka v klinicheskoj praktike. Molekuljarnaja biologija. 2015; 49 (4): 531–40 (in Russian)]
  14. Chomczynski P., Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc. 2006; 1 (2): 581–5.
  15. Livak K.J., Schmittgen T.D. Methods. 2001; 25: 402–8.
  16. Gmurman V.E. Teoriya veroyatnostey i matematicheskaya statistika. M.: Vysshaya shkola, 2004; 479.
  17. [Gmurman V.E. Teorija verojatnostej i matematicheskaja statistika. M.: Vysshaja shkola, 2004; 479 (in Russian)]
  18. Gubler E.V., Genkin A.A. Primenenie neparametricheskih kriteriev statistiki v mediko-biologicheskih issledovaniyah. L., 1973.
  19. [Gubler E.V., Genkin A.A. Primenenie neparametricheskih kriteriev statistiki v mediko-biologicheskih issledovanijah. L., 1973 (in Russian)]
  20. Zhou J.H., Chen H.Z., Ye F., Lu W.G., Xie X. Fasmediated pathway and apoptosis in normal cervix, cervical intraepithelial neoplasia and cervical squamous cancer. Oncol Rep. 2006; 16 (2): 307–11.
  21. Kovchur P.I., Bahidze E.V., Kurmyshkina O.V., Volkova T.O. Issledovanie pokazateley apoptoza u bol`nyh s preinvazivnym i invazivnym rakom sheyki matki. Opuholi zhenskoy reproduktivnoy sistemy. 2015; 1: 61–8.
  22. [Kovchur P.I., Bahidze E.V., Kurmyshkina O.V., Volkova T.O. Issledovanie pokazatelej apoptoza u bol'nyh s preinvazivnym i invazivnym rakom shejki matki. Opuholi zhenskoj reproduktivnoj sistemy. 2015; 1: 61–8 (in Russian)]