Bioanalytical study of tumour markers for prostate carcinoma at RNA and protein level

Česká verzia

Authors: J. Gumulec ¹; M. Masařík ¹; S. Křížková ²; P. Babula ²; R. Hrabec ³; A. Rovný ³; M. Masaříková ²; V. Adam ²; T. Eckschlager ⁴; R. Kizek ²
Authors place of work: Masarykova univerzita Brno, Lékařská fakulta Ústav patologické fyziologie Přednostka: prof. MUDr. Anna Vašků, CSc. ¹; Mendelova univerzita v Brně, Agronomická fakulta Ústav chemie a biochemie Vedoucí: doc. RNDr. Petr Hrdlička, CSc. ²; Fakultní nemocnice u sv. Anny v Brně Urologické oddělení Primář: MUDr. Arne Rovný ³; 2. Lékařská fakulta Univerzita Karlova a Fakultní nemocnice Motol, Praha Klinika dětské hematologie a onkologie Přednosta: prof. MUDr. Jan Starý, DrSc. ⁴
Published in the journal: Prakt. Lék. 2011; 91(8): 471-476
Category: Of different specialties

Summary

Current methods for diagnosis of prostate carcinoma do not enable us to distinguish aggressive tumours (significant tumours) from clinically latent tumours (non-significant tumours). This study aims to determine levels of potential clinically important tumour markers such as

alpha-methyl CoA-racemase (AMACR),
caveolin-1,
metallothionein (MT),
p53,
NF-κB,
c-FOS,
c-JUN,
Ki-67,
prostate-specific antigen (PSA),
ZIP1 and ZnT-1 in prostatic tissue represented by 22Rv1 (tumour) and PNT1A (healthy) cell lines and in blood serum of patients with histologically evaluated adenocarcinoma (82 tumour patients and 51 healthy volunteers).

Based on mRNA expression, it was found that Cav-1, NF-κB, c-FOS and c-JUN were down-regulated and MT, AMACR, PSA, Ki-67, MMP-9 and zinc transporters ZIP1 and ZnT-1 were up-regulated.

In serum, the level of MT was significantly enhanced above 1 μM. Caveolin-1 levels were significantly increased in high-grade tumours, which points to the possibility of using this protein as a marker for the aggressive form of prostate carcinoma.

Key words:
tumour diseases, polymerase chain reaction, electrochemistry, immunodetection, molecularly-biological techniques, tumour markers.

Zdroje

1. Abate-Shen, C., Shen, M.M. Molecular genetics of prostate cancer. Genes Dev. 2000, 14(19), p. 2410-2434.

2. Adam, V., Baloun, J., Fabrik, I. et al. An electrochemical detection of metallothioneins at the zeptomole level in nanolitre volumes. Sensors 2008, 8(4), p. 2293-2305.

3. Adam, V., Blastik, O., Krizkova, S. et al. Application of the Brdicka reaction in determination of metallothionein in patients with tumours. Chem. Listy 2008, 102(1), p. 51-58.

4. Adam, V., Fabrik, I., Eckschlager, T. et al. Vertebrate metallothioneins as target molecules for analytical techniques. Trends Anal. Chem. 2010, 29(5), p. 409-418.

5. Adam, V., Petrlova, J., Wang, J. et al. Zeptomole electrochemical detection of metallothioneins. PLoS One, 2010, 5(7): e11441. doi:10.1371/journal.pone.0011441.

6. Azzazy, H.M.E., Mansour, M.M.H., Kazmierczak, S.C. Nanodiagnostics: A new frontier for clinical laboratory medicine. Clin. Chem. 2006, (52(7), p. 1238-1246.

7. Babula, P., Kohoutkova, V., Opatrilova, R. et al. Pharmaceutical importance of zinc and metallothionein in cell signalling. Chimica Oggi-Chemistry Today, 2010, 28(6), p. 18-21.

8. Bartek, J., Hamerlik, P., Lukas, J. On the origin of prostate fusion oncogenes. Nature Genet., 2010, 42(8), p. 647-648.

9. de Wit, R., Sternberg, C.N. Cancers of the Genitourinary Tract. In Cavalli, F. et al. Textbook of medical oncology. London: Informa Healthcare, 2009.

10. Dusek, L., Abrahamova, J., Lakomy, R. et al. Multivariate analysis of risk factors for testicular cancer: A hospital-based case-control study in the Czech Republic. Neoplasma, 2008, 55(4), p. 356-368.

11. Dušek, L., Mužík, J., Gelnarová, E., et al. Incidence a mortalita nádorových onemocnění v České republice. Klin. Onkol. 2010, 23(5), s. 311-324.

12. Eckschlager, T., Adam, V., Hrabeta, J. et al. Metallothioneins and cancer. Curr. Protein Pept. Sci. 2009, 10(4), p. 360-375.

13. Edwards, J., Krishna, N.S., Mukherjee, R., Bartlett, J.M.S. The role of c-Jun and c-Fos expression in androgen-independent prostate cancer. J. Pathol. 2004, 204(2), p. 153-158.

14. Evans, A.J. Alpha-Methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies. J. Clin. Pathol. 2003, 56(12), p. 892-897.

15. Fabrik, I., Adam, V., Křížková, S. et al. Určení hladiny termostabilních thiolů u pacientů se zhoubným nádorem. Klin. Onkol. 2007, 20(6), s. 384-389.

16. Fabrik, I., Kukačka, J., Adam, V. a kol. Metalothionein a jeho vztah k protinádorové léčbě na bázi platinových komplexů. Prakt. Lék. 2008, 88(2), s. 90-93.

17. Fiala, R., Ženíšek, J. Adenokarcinom prostaty a screening. Prakt. Lék. 2001, 81(11), s. 613-618.

18. Foltýn, I. Aktivní vyhledávání karcinomu prostaty na základě vyšetření PSA v ordinaci praktického lékaře. Prakt. Lék. 2007, 87(2), s. 117-118.

19. Formigari, A., Irato, P., Santon, A. Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: Biochemical and cytochemical aspects. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 2007, 146(4): p. 443-459.

20. Gao, X., Porter, A.T., Grignon, D.J. et al. Diagnostic and prognostic markers for human prostate cancer. Prostate 1997, 31(4), p. 264-281.

21. Gioeli, D. Signal transduction in prostate cancer progression. Clin. Sci. 2005, 108(4), s. 293-308.

22. Grepl, M., Student, V., Furst, T., Furstova, J. Prostate cancer detection yield in repeated biopsy is independent of the diagnosis of earlier biopsies. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub., 2009, 153(4), p. 297-302.

23. Gumulec, J., Masařík, M., Hrabec, R. a kol. Zinek a jeho vztah k nádorům prostaty. Prakt. Lék., 2010, 90(8), s. 455-459.

24. Horáková, Z., Tóthová, E., Salzman, R. a kol. Význam elevace hladin metalothioneinu v krvi u pacientů s nádory hlavy a krku – 2. část. Otorinolaryng. a Foniat. 2008, 57(2), s. 90-97.

25. Housa, D., Vernerová, Z., Heráček, J. et al. Serum resistin levels in benign prostate hyperplasia and non-metastatic prostate cancer: Possible role in cancer progression. Neoplasma, 2008, 55(5), p. 442-446.

26. Humbert, L., Chevrette, M. Somatic molecular genetics of prostate cancer. In Foulkes, et al. Male reproductive cancers epidemiology, pathology and genetics. New York, Dordrecht, Heidelberg, London: Springer Verlag, 2009.

27. Chi, S.G., White, R.W.D., Meyers, F.J. et al. P53 in prostate cancer frequent expressed transition mutations. J. Natl. Cancer Inst., 1994, 86(12), p. 926-933.

28. Jamaspishvili, T., Kral, M., Khomeriki, I. et al. Urine markers in monitoring for prostate cancer. Prostate Cancer Prostatic Dis. 2010, 13(1), p. 12-19.

29. Kerbel, R.S. Molecular origins of cancer: Tumor angiogenesis. New Engl. J. Med. 2008, (358(19), p. 2039-2049.

30. Kizek, R., Vacek, J., Adam, V., Vojtěšek, B. Vztah metalothioneinu k rakovině a protinádorové léčbě. Klin. Biochem. Metabol. 2004, 12(2), s. 72-78.

31. Kizek, R., Vacek, J., Trnkova, L. et al. Application of catalytic reactions on a mercury electrode for electrochemical detection of metallothioneins. Chem. Listy, 2004, 98(4), p. 166-173.

32. Král, M., Rosinská, V., Student, V. et al. Genetic determinants of prostate cancer: A review. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2011, 155(1), p. 3-10.

33. Krizkova, S., Fabrik, I., Adam, V. et al. Metallothionein - a promising tool for cancer diagnostics. Bratisl. Lek. Listy, 2009, 110(2), p. 93-97.

34. Lukeš, M., Záleský, M., Heráček, J. a kol. P53 a karcinom prostaty. Klin. Onkol., 2003, 16(3), s. 141-144.

35. Milon, B.C., Agyapong, A., Bautista, R. et al. Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells. Prostate 2010, 70(3), p. 288-296.

36. Mlcochova, P., Barinka, C., Tykvart, J. et al. Prostate-specific membrane antigen and its truncated form PSM′. Prostate 2009, 69(5), p. 471-479.

37. Moul, J.W. Prostate specific antigen only progression of prostate cancer. J. Urol. 2000, 163(6), p. 1632-1642.

38. Ondrušová, M., Mužík, J., Kliment, J. a kol. Incidencia a mortalita na karcinom prostaty vo vybraných krajinách strednej Europy. Klin. Onkol., 2011, 24(2), s. 126-132.

39. Petrlová, J., Blaštík, O., Průša, R. et al. Analýza obsahu metatothioneinu u pacientů se zhoubným nádorem prsu, tlustého střeva a nebo melanomem. Klin. Onkol., 2006, 19(2), s. 138-142.

40. Polascik, T.J., Oesterling, J.E., Partin, A.W. Prostate specific antigen: A decade of discovery - What we have learned and where we are going. J. Urol., 1999, 162(2), p. 293-306.

41. Rubin, M.A., Zhou, M., Dhanasekaran, S.M., et al. Alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 2002, 287(13), p. 1662-1670.

42. Schroeder, F.H., Hugosson, J., Roobol, M.J. et al. Screening and prostate-cancer mortality in a randomized European study. N. Engl. J. Med., 2009, 360(13), p. 1320-1328.

43. Sramkoski, R.M., Pretlow, T.G., Giaconia, J.M. et al. A new human prostate carcinoma cell line, 22Rv1. In Vitro Cell. Dev. Biol. Anim. 1999, 35(7), p. 403-409.

44. Štern, P., Vranovský, K., Šafarčík, K. Karcinom prostaty – molekulární podstata, diagnostika a ekonomika prevence. Klin. Biochem. Metabol., 2008, 16(1), s. 19-26.

45. Študent, V., Grepl, M., Král, M., Hartmann, I. Má vyšetření PSA stále význam při vyhledávání karcinomu prostaty? Urol. Prax., 2006, 5(5), s. 214-218.

46. Thiagalingam, A., DeBustros, A., Borges, M. et al. RREB-1, a novel zinc finger protein, is involved in the differentiation response to ras in human medullary thyroid carcinomas. Mol. Cell. Biol., 1996, 16(10), p. 5335-5345.

47. Thomson, J.O., Dzubak, P., Hajduch, M. Prostate cancer and the food supplement, PC-SPES: Minireview. Neoplasma, 2002, 49(2), p. 69-74.

48. Webber, M.M., Bello, D., Quader, S. Immortalized and tumorigenic adult human prostatic epithelial cell lines: Characteristics and applications. 3. Oncogenes, suppressor genes, and applications. Prostate 1997, 30(2), p. 136-142.

49. Zelená, J., Potěšil, D., Vacek, J. et al. Metalothionein jako prognostický marker nádorového onemocnění. Klin. Onkol., 2004, 17(6), s. 190-195.