GENE EXPRESSION OF POLYAMINE METABOLISM PROTEINS IN HUMAN PROSTATE CANCER AND BENIGN PROSTATIC HYPERPLASIA

Authors

  • V.V. Bentrad R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
  • S.P. Zaletok R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
  • O.О. Klenov R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
  • Yu.V. Vitruk National Cancer Institute, Kyiv, Ukraine
  • Е.О. Stakhovsky National Cancer Institute, Kyiv, Ukraine

DOI:

https://doi.org/10.32471/oncology.2663-7928.t-22-1-2020-g.8739

Keywords:

benign prostate hyperplasia, ornithine-decarboxylase, polyamines, prostate cancer, spermine acetyltransferase, spermine synthase

Abstract

Prostate cancer and benign prostatic hyperplasia are currently the most common oncopathologies of older men. Recent studies suggest that the metabolism of polyamines in prostate tumors differs in tumors of other locations. Objective: to investigate the gene expression of polyamines biosynthesis enzymes — ornithine decarboxylase and spermine synthase — and, spermine catabolism enzyme — acetyltransferase in malignant and benign prostate cancer cells. Object and methods: the study was performed on 25 postoperative samples of tumors from patients with prostate cancer (PC) and benign prostatic hyperplasia (BHP): 7 samples of benign and 18 samples of malignant tumors. The gene expression was determined using biochemical, immunological and molecular methods. Results: The decreased level of ornithine decarboxylase expression in malignant prostate tumors was determined compared with benign tumors. It is shown that the level of spermine synthase in malignant prostate tumors, in contrast to benign, detected only in trace amounts. However, the level of expression of spermine acetyltransferase in malignant prostate tumors was higher compared with benign tumors and increased with disease progression. Conclusion: the results indicate the diversity of changes in polyamine metabolism in benign and malignant prostate cancer tumors. The obtained data can be further used for accurate diagnosis of prostate cancer and for the search of targeted anticancer drugs.

 

References

Lima AR, Bastos Mde L, Carvalho M, Guedes de Pinho P. Biomarker discovery in human prostate cancer: an update in metabolomics studies. Transl Oncol 2016; 9 (4): 357–70.

Stakhovsky EA, Fedorenko ZP, Vitruk YuV, et al. Prostate cancer screening. Clin Oncol 2016; (1): 50–3 (in Russian).

Lawrentschuk N, Perera M. Benign prostate disorders. Chapter 9. Endotext. MDTEXT.COM, 2016. 77 p.

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394–424.

Cancer in Ukraine, 2018–2019. Incidence, mortality, activities of oncological service. Bull Natl Cancer Register Ukr; Kyiv, 2020; 21: 82 p. (in Ukrainian).

Berdinsky NK, Zaletok SP. Polyamines and tumor growth. Naukova Dumka, Kyiv, 1987, 141 p. (in Russian).

Zaletok SP. Polyamines — markers of tumor growth and targets for anticancer therapy. Thesis for the degree of Doctor of Biological Sciences (D. Biol. Sci.) speciality 14.01.07 — oncology. Kyiv, 2007. 37 p. (in Ukrainian).

Zaletok SP. The role of polyamines in carcinogenesis and tumor growth. Oncology. Selected lectures for students and doctors ed. VF Chekhun. Kyiv, 2010: 354–70 (in Ukrainian).

Soda K. The mechanisms by which polyamines accelerate tumor spread. J of Exp and Clin Cancer Research 2011; 30: 95–104.

Nowotarski SL, Woster PM, Casero RA Jr. Polyamines and cancer: implications for chemotherapy and chemoprevention. Expert RevMol Med 2013, 15: e3. doi: 10.1017/erm.2013.3.

Kusano T, Suzuki H. (eds.). Polyamines. A Universal molecular nexus for growth, survival, and specialized metabolism. Springer Tokyo Heidelberg New York Dordrecht London. Springer Japan 2015: 330 p.

Palavan-Unsal N, Aloglu-Senturk SM, Arısan D. The function of polyamine metabolism in prostate cancer. Exp Oncol 2006; 28: 178–86.

Stacy M. Lloyd, James A, and Sreekumar A. Metabolomic profiling of hormone-dependent cancers: a bird’s eye view. Trends in Endocrinol Metab 2015; 30: 1–9.

Simoneau AR, Gerner EW, Mai Phung, et al. α-Difluoromethylornithine and polyamine levels in the human prostate: results of a phase IIа trial. J Natl Cancer Inst 2001; 93: 57–9.

Battaglia V, Destefano Shields C, Murray-Stewart T, Casero RA Jr. Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention. Amino Acids 2013; 46: 511–9.

Sovak M, Bellas R, Kim D, et al. Aberrant nuclear factor-kB/Rel

expression and pathogenesis of breast cancer. J Clin Invest 1997; 100: 2952–60.

Bradford M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–5.

Young L, Salomon R, Au W, et al. Ornithine decarboxylase (ODC) expression pattern in human prostate tissues and ODC transgenic mice. J Histochem Cytochem 2006; 54 (2): 223–9.

Huang W, Eickhoff JC, Ghomi FM, et al. Expression of spermidine/spermine N1-acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis. Prostate 2015; 75: 1150–9.

Zaletok SP, Klenov OO, Gogol SV, et al. Blood and urine polyamines as new diagnostic markers of prostate cancer. Oncology 2019; 21: 220–3 (in Ukrainian).

Van der Graaf M, Schipper RG, Oosterhof GO, et al. Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer. MAGMA 2000; 10 (3): 153–9.

Zaletok SP, Shlykhovenko VO, Stakhovsky EO, et al. Polyamines and ribonuclease as markers for differential diagnosis and prognosis of prostate cancer. Guidelines. Kyiv, Ukraine. 2018 (in Ukrainian).

Affronti HC, Rowsam AM, Pellerite AJ, et al. Pharmacological polyamine catabolism upregulation with methionine salvage pathway inhibition as an effective prostate cancer therapy. Nat Commun 2020; 11 (1): 52.

Published

2020-07-01

How to Cite

Bentrad , V., Zaletok , S., Klenov , O., Vitruk , Y., & Stakhovsky Е. (2020). GENE EXPRESSION OF POLYAMINE METABOLISM PROTEINS IN HUMAN PROSTATE CANCER AND BENIGN PROSTATIC HYPERPLASIA. Oncology, 22(1-2), 32–35. https://doi.org/10.32471/oncology.2663-7928.t-22-1-2020-g.8739

Issue

Section

Original investigations