The role of transcription and growth factors in the development of the tumor pathology of the prostate gland


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Abstract

Introduction. The molecular mechanisms of the development of the prostate tumor pathology are associated with the activation of both androgen-dependent and androgen-independent signaling pathways, accompanied by the development of chronic inflammation and hypoxia. However, the role of transcription and growth factors in the initiation of prostate tumor changes is not investigated The aim of the study was to investigate the expression of transcription and growth factors in the tissue of prostate cancer (PCa) cases and patients with benign hyperplasia (BH). Material and methods. 97 patients with prostate pathology were included in the study. They received treatment in the Department of General Oncology of the Cancer Research Institute of the Tomsk National Research Medical Center. 42 patients had BH, in 55 patients T2-3N0M0 was verified due to locally advanced PCa. The PSA level and the amount of testosterone in the serum were determined by ELISA. The expression of nuclear factors NF-κBp65, NF-κBp50, HIF-1, HIF-2, growth factors VEGF, VEGFR2, CAIX was investigated by PCR in real-time.Results. In PCa patients PSA and testosterone levels in with prostate cancer were revealed to be declined if compared with BH cases. The growth of the nuclear factor NF-κBp65 with a decrease in nuclear factors activated by hypoxia (HIF-1, HIF-2) was observed in PCa tissues, compared with BH patients. At the same time, an increase in VEGFR2 expression with a decrease in the level of CAIX mRNA in the transformed tissues was detected. Conclusion. The study shows the multidirectional nature of changes in the level of PSA and testosterone with the severity of the prostate tumor pathology. The formation of inflammatory responses with an increase in the NF-κBp65 expression and the VEGFR2 growth is significant for the malignant transformation of prostate cells. At the same time, the development of hypoxia and the increase in the expression of factors HIF-1, HIF-2 were recorded in BH patients.

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About the authors

L. V Spirina

Cancer Research Institute, Tomsk National Research Medical Center; Siberian State Medical University

Email: spirinalvl@mail.ru
Kooperativny street, 5, Tomsk, 634050, Russian Federation; Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

I. V Kovaleva

Siberian State Medical University

Email: spirinalvl@mail.ru
Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

D. A Fedotov

Siberian State Medical University

Email: spirinalvl@mail.ru
Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

A. K Gorbunov

Cancer Research Institute, Tomsk National Research Medical Center

Email: spirinalvl@mail.ru
Kooperativny street, 5, Tomsk, 634050, Russian Federation

E. A Usynin

Cancer Research Institute, Tomsk National Research Medical Center

Email: spirinalvl@mail.ru
Kooperativny street, 5, Tomsk, 634050, Russian Federation

E. M Slonimskaya

Cancer Research Institute, Tomsk National Research Medical Center; Siberian State Medical University

Email: spirinalvl@mail.ru
Kooperativny street, 5, Tomsk, 634050, Russian Federation; Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

I. V Kondakova

Cancer Research Institute, Tomsk National Research Medical Center

Email: spirinalvl@mail.ru
Kooperativny street, 5, Tomsk, 634050, Russian Federation

D. A Dyakov

Siberian State Medical University

Email: spirinalvl@mail.ru
Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

References

  1. Austin D.C., Strand D.W, Love H.L., Franco O.E., Jang A., Grabowska M.M., Miller N.L., Hameed O., Clark P.E., Fowke J.H., Matusik R.J., Jin R.J. NF-kB and androgen receptor variant expression correlate with human BPH progression. Prostate. 2015;
  2. Meyer A.R., Gorin M.A. First point-of-care PSA test for prostate cancer detection. Nat. Rev Urol. 2019. https://doi. org/10.1038/s41585-019-0179-1
  3. Albuquerque G.A.M., Guglielmetti G.B., Barbosa A., Pontes J., Fazole A., Cordeiro M., Coelho R., Carvalho P.A., Gallucci F., Padovani J., Park R., Cury J., Nonemacher H., Srougi M., Nahas W. Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer. Rev. Assoc. Med. Bras. 2017; 63 (8): 704-10. http:// dx.doi.org/10.1590/1806-9282.63.08.704.
  4. Kim H.J., Park J.W, Cho Y.S., Cho C.H., Kim J.S., Hyun-Woo Shin, Chung D.H., Kim S.J., Chun Y.S. Pathogenic role of HIF-1a in prostate hyperplasia in the presence of chronic inflammation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2013; 1832 (1): 183-94. https://doi. org/10.1016/j.bbadis.2012.09.002.
  5. Deep G., Panigrahi G.K. Hypoxia-Induced Signaling Promotes Prostate Cancer Progression: Exosomes Role as Messenger of Hypoxic Response in Tumor Microenvironment. Crit Rev Oncog. 2015; 20 (5-6): 419-34. https://doi.org/10.1615/CritRevOn-cog.v20.i5-6.130.
  6. Chen Y, Xu H., Shi Q., Gu M., Wan X., Chen Q.,Wang Z. Hypoxia-inducible factor 1a (HIF-1a) mediates the epithelial-mesenchymal transition in benign prostatic hyperplasia. Int. J. Clin. Exp. Pathol. 2019; 12 (1): 295-304.
  7. Kruslin B., Tomas D., Dzombeta T, Milkovic-Perisa M., Ulamec M. Inflammation in Prostatic Hyperplasia and Carcinoma-Basic Scientific Approach. Front Oncol. 2017; 7: 77. https://doi.org/10.3389/ fonc.2017.00077
  8. Verzella D., Fischietti M., Capece D., Vecchiotti D., Del Vecchio F., Cicciarelli G., Mastroiaco V, Tessitore A., Alesse E., Zazzeroni F. Targeting the NF-kB pathway in prostate cancer: a promising therapeutic approach. Curr. Drug Targets. 2016; 17 (3): 311-20.
  9. Jain G., Voogdt C., Tobias A., Spindler K.-D., Moller P, Cronauer M.V., Marienfeld R.B. IkB kinases modulate the activity of the androgen receptor in prostate carcinoma cell lines. Neoplasia. 2012; 14: 178-89. https:// doi.org/10.1593/neo.111444.
  10. Mehraein-Ghomi F., Church D.R., Schreiber C.L., Weichmann A.M., Basu H.S., Wilding G. Inhibitor of p52 NF-kB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated AR (ser81). Genes Cancer. 2015; 6: 428-44. https://doi. org/10.18632/genesandcancer.77
  11. Jin R.J., Lho Y, Connelly L., Wang Y, Yu X., Saint Jean L, Case T.C., Ellwood-Yen K., Sawyers C.L., Bhowmick N.A., Blackwell T.S., Yull F.E., Matusik R.J. The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Res. 2008; 68 (16): 6762-9. https://doi.org/10.1158/0008-5472. CAN-08-0107
  12. Nelius T, Filleur S., Yemelyanov A., Budunova I., Shroff E., Mirochnik Y, Aurora A., Veliceasa D., Xiao W, Wang Z., Volpert O.V. Androgen receptor targets NFkappaB and TSP1 to suppress prostate tumor growth in vivo. Int. J. Cancer. 2007; 121: 999-1008. https://doi.org/10.1002/ijc.22802
  13. Lessard L., Saad F, Le Page C., Diallo J.-S., Peant B., Delvoye N., Mes-Masson A.-M. NF-kappaB2 processing and p52 nuclear accumulation after androgenic stimulation of LNCaP prostate cancer cells. Cell. Signal. 2007; 19: 1093-100. https://doi. org/10.1016/j.cellsig.2006.12.012
  14. Cui Y, Nadiminty N., Liu C., Lou W, Schwartz C.T., Gao A.C. Upregulation of glucose metabolism by NF-kB2/p52 mediates enzalutamide resistance in castration-resistant prostate cancer cells. Endocr. Relat. Cancer. 2014; 21 (3): 435-42. https:// doi.org/10.1530/ERC-14-0107
  15. Wu F, Ding S., Li X., Wang H., Liu S., Wu H., Bi D., Ding K., Lu J. Elevated expression of HIF-la in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia. Oncotarget. 2016;
  16. Huang M., Du H., Zhang L., Che H., Liang C. The association of HIF-1a expression with clinicopathological significance in prostate cancer: a meta-analysis. Cancer Manag Res. 2018; 10: 2809-16. https://doi. org/10.2147/CMAR.S161762
  17. Grivas N., Goussia A., Stefanou D., Giannakis D. Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer. Cent. European J. Urol. 2016; 69 (1): 63-71. https://doi.org/10.5173/ceju.2016.726
  18. Cansino J.R., Vera R., Rodriguez de Bethen-court F, Bouraoui Y, Rodriguez G., Prieto A., de la Pena J., Paniagua R., Royuela M. Prostate specific antigen and NF-kB in prostatic disease: relation with malignancy. Actas. Urol. Esp. 2011; 35 (1): 16-21. https:// doi.org/10.1016/j.acuro.2010.08.002
  19. Gautam K.A., Singh A.N, Srivastav A.N., Sankhwar S.N. Angiogenesisinprostate-cancerandbenignprostatichyperpla-siaassessedby VEGF and CD-34 IHC: A comparative clinico-pathological study. Afr. J. Urol. 2018; 24 (2): 98-103.
  20. Спирина Л.В., Тарасенко Н.В., Горбунов А.К., Кондакова И.В., Слонимская Е.М., Усынин Е.А. Экспрессия молекулярных маркеров в ткани рака предстательной железы: связь с клиникоморфологическими особенностями заболевания. Медицинская генетика. 2018; 17 (3): 18-22.
  21. Спирина Л.В., Горбунов А.К., Кондакова И.В., Слонимская Е.М., Усынин Е.А., Тарасенко Н.В. Экспрессия транскрипционного фактора TRIM16 в ткани рака предстательной железы, связь с экспрессией эстрогеновых и андрогеновых рецепторов и клиникоморфологическими особенностями заболевания. Бюллетень сибирской медицины. 2018; 17 (3): 122-30. https://doi. org:10.20538/1682-0363-2018-3-122-130
  22. Staal J., Beyaert R. Inflammation and NF-kB signaling in prostate cancer: mechanisms and clinical implications. Cells. 2018; 7 (9). https://doi.org/10.3390/ cells7090122.
  23. Ambrosio M. R., Di Serio C., Danza G., Rocca B.J., Ginori A., Prudovsky I., Marchionni N., Del Vecchio M.T., Tarantini F Carbonic anhydrase IX is a marker of hypoxia and correlates with higher Gleason scores and ISUP grading in prostate cancer. Diagn Pathol. 2016; 11 (1): 45. https://doi. org/10.1186/s13000-016-0495-1
  24. Smyth L.G., O'Hurley G., O'Grady A., Fitzpatrick J.M., Kay E., Watson R.W. Carbonic anhydrase IX expression in prostate cancer. Prostate Cancer Prostatic Dis. 2010; 13 (2): 178-81. https://doi.org/10.1038/ pcan.2009.58

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