Features of some transcription factors gene expression in the malignancy tissues of the corpus uteri
https://doi.org/10.17650/2313-805X-2019-6-1-57-62
Abstract
Background. Worldwide, more than 300,000 women are diagnosed with uterine cancer each year. Currently, the problem of finding highly specific molecular tumor markers for this disease remains relevant. Screening for gene expression of transcription factors responsible for controlling the differentiation of cells of endometrial tissues may allow the formation of a tumor markers panel and explore the fundamental mechanisms of oncotransformation.
Objective of our study was to analyze changes in the expression of transcription factors OCT4, SOX2 and C-MYC in the tissues of the uterus (corpus uteri) during the process of their malignancy.
Materials and methods. Uterus tissue biopsy specimens of 45 patients (tumor and non-tumor) were used for the study. To determine the relative expression of 3 genetic loci encoding the transcription factors OCT4, SOX2 and C-MYC the real-time polymerase chain reaction method, ACTB was used as the reference gene.
Results. A change of OCT4, SOX2 and C-MYC genes transcriptional activity in uterus tumor cells is found as the tumor develops. By reducing the tumor cells differentiation degree expression of OCT4 gene increases most significantly, that confirmsits status of undifferentiated cellsmarker. As the differentiation degree of tumor cells decreases, OCT4, SOX2 and C-MYC genes expression change affects the adjacent conditionally normal tissue of the uterus, but with less intensity, especially in the later stages of malignancy.
Conclusion. The obtained data makes it possible to use the OCT4, SOX2 and C-MYC genes as differential markers of the tumor process development, and the SOX2 gene expression as a predictive marker of malignancy.
About the Authors
D. S. Kutilin
Rostov Research Institute of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
63 14th Line, Rostov-on-Don 344037.
I. S. Nikitin
Rostov Research Institute of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
63 14th Line, Rostov-on-Don 344037.
O. I. Kit
Rostov Research Institute of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
63 14th Line, Rostov-on-Don 344037.
References
1. Kit O.I., Vodolazhsky D.I., Kutilin D.S. Aberrant transcriptional activity of apoptosis-regulating genes in malignant neoplasm of corpus uteri. Molekulyarnaya meditsina = Molecular Medicine 2018;16(1):25—31 (In Russ.).
2. Pitynski K., Banas T., Pietrus M. et al. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading. Int J Clin Exp Pathol 2015;8(7):8189—98.
3. Kit O.I., Vodolazhsky D.I., Kutilin D.S. et al. Changes in expression of estrogen-regulatory genes in malignancy uterine tis¬sues. Kubanskiy nauchnyy meditsinskiy vestnik = Kuban Scientific Medical Bulletin 2016;(2):84—90. (In Russ.).
4. Zhu C.Q., Shih W., Ling C.H., Tsao M.S. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol 2006;59(8):790-800. DOI: 10.1136/jcp.2005.031351. PMID: 16873561.
5. Chen Z., Xu W.R., Qian H. et al. Oct4, a novel marker for human gastric cancer. J Surg Oncol 2009;99(7):414—19. DOI: 10.1002/jso.21270. PMID: 19347886.
6. Masui S., Nakatake Y., Toyooka Y. et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 2007;9(6):625—35. DOI: 10.1038/ncb1589. PMID: 17515932.
7. Gearhart J., Pashos E.E., Prasad M.K. Pluripotency redux — advances in stem-cell research. N Engl J Med 2007;357(15):1469—72. DOI: 10.1056/NEJMp078126. PMID: 17928593.
8. Chen Y., McGee J., Chen X. et al. Identification of druggable cancer driver genes amplified across T CGA datasets. PLoS One 2014;9(5):e98293. DOI: 10.1371/journal.pone.0107646. PMID: 24874471.
9. Kit O.I., Vodolazhsky D.I., Kutilin D.S. et al. Method of recurrent endometrial cancer prediction based on PTEN and CYP1B1 genes expression level. Patent for invention RUS 2605302, 10.11.2015. (In Russ.).
10. Kutilin D.S. Molecular mechanisms for the implementation of geroprotective activity of the delta-sleep peptide. Author’s abstract of thesis ... of candidate iological sciences: 03.01.04. South Federal University. Rostov-on-Don, 2013. (In Russ.).
11. Kit O.I., Vodolazhsky D.I., Dimitriadi S.N. et al. The activity of proapoptotic genes increases after renal ischemia/reperfusion. Molekulyarnaya biologiya = Molecular Biology 2017;51(3):445—52. (In Russ.).
12. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25(4):402-8. DOI: 10.1006/meth.2001.1262. PMID: 11846609.
13. Hubbard S., Gargett C. A cancer stem cell origin for human endometrial carcinoma? Reproduction 2010;140(1):23—32. DOI: 10.1530/REP-09-0411. PMID: 20089663.
14. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. PMID: 16904174.
15. Rizzino A. The Sox2-Oct4 connection: critical players in a much larger interdependent network integrated at multiple levels. Stem Cells 2013;31(6):1033—9. DOI: 10.1002/stem.1352. PMID: 23401375.
16. You L., Guo X., Huang Y. Correlation of cancer stem-cell markers OCT4, SOX2, and NANOG with clinicopathological features and prognosis in operative patients with rectal cancer. Yonsei Med J 2017;59(1):35—42. DOI: 10.3349/ymj.2018.59.1.35. PMID: 29214774.
17. Hatefi N., Nouraee N., Parvin M. et al. Evaluating the expression of OCT4 as a prognostic tumor marker in bladder cancer. Iran J Basic Med Sci 2012;15(6):1154—61. PMID: 23653844.
18. Lee C.J., Sung P.L., Kuo M.H. et al. Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma. Sci Rep 2018;8(1):17550. DOI: 10.1038/s41598-018-35592-0. PMID: 30510261.
Review
For citations:
Kutilin D.S., Nikitin I.S., Kit O.I. Features of some transcription factors gene expression in the malignancy tissues of the corpus uteri. Advances in Molecular Oncology. 2019;6(1):57-62. (In Russ.) https://doi.org/10.17650/2313-805X-2019-6-1-57-62
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