Expression of SHB in prostate cancer tissue: its role in the diagnostics and prognostics
Authors:
Marek Schmidt 1; Jaroslav Mareš 2; Ladislav Jarolím 1; Michal Černý 3; Štěpán Veselý 1; Marek Babjuk 1
Authors‘ workplace:
Urologická klinika 2. LF UK a FN Motol
Praha
1; Ústav biologie a lékařské genetiky 2. LF UK
a FN Motol, Praha
2; Přírodovědecká fakulta JČU
České Budějovice
3
Published in:
Ces Urol 2012; 16(1): 58-66
Category:
Original article
Overview
Aim:
Among urological malignancies prostate cancer most frequently leads to death. The etiology of this disease remains unknown. Many analyses identified genes associated with increased susceptibility to prostate cancer, where changes in gene expression were associated with prostate cancer. Adaptor protein SHB is involved in apoptosis, angiogenesis and cell cycle regulation systems. A correlation between the expression of SHB, and reduced proliferation of prostate cancer PC3 cells was detected. The aim of this work was to compare SHB expression in prostate cancer to that in benign prostate hyperplasia and to evaluate its diagnostic and prognostic potential.
Methods:
In 2008–2010, isolation of mRNA from prostate cancer was performed in 53 patients. Twenty four patients with benign prostate hyperplasia were used as a control group. The identical procedure of mRNA isolation using Oligotex Direct mRNA Midi/Maxi was used. RTPCR, expression of specific sample was visualized by electrophoresis. Optical density was measured with densitometry. For relative expression calculation, housekeeping gene GAD (glyceraldehyde-3-phosphate dehydrogenase) was used. Results have been evaluated statistically.
Results:
Statistically significant decrease in relative expression of SHB in prostate cancer tissue was detected (p < 0.001). In a comparison of patients with localized (T2) and locally advanced tumor, we observed a trend of decreased expression in locally advanced disease which had not achieved statistic significance (p < 0.0693). A comparison between groups detected no differences in the Gleason score (GS < 7 and GS ≥ 7).
Conclusion:
SHB is a candidate gene for prostate cancer development. Its expression is decreased in prostate cancer compared to benign prostate hyperplasia. Its levels are decreased in locally advanced stages.
Key words:
gene expression, prostate cancer, radical prostatectomy, SHB.
Sources
1. Klečka J, Hora M, Holubec L, Pešta M, Topolčan O, Eret V, Chottová-Dvořáková M, Babjuk M, Novák K, Stolz J. Exprese DD3PCA3 (Diff erencial Display Code 3) mRNA ve tkáni prostaty u pacientů s karcinomem prostaty a benigní hyperplazií prostaty. Ces Urol 2010; 14(1): 39–47.
2. Chen L, Hong C, Chen EC, Yee SW, Xu L, Almof EU, Wen C, Fuji K, Johns SJ, Stryke D, Ferrin TE, Simko J, chen X, Costello JF, Giacomini KM. Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. Pharmacogenomics J 2012 Jan 10. doi: 10.1038/ tpj.2011.60. [Epub ahead of print]
3. Hahn WC, Weinberg RA. Modelling the molecular circuity of cancer. Nat Rev Cancer 2002; 2: 331–341.
4. Štern P, Vranovský K, Šafarčík K. Karcinom prostaty – molekulární podstata, diagnostika a ekonomika prevence. Klin Biochem Met 2008; 16(37): 19–26.
5. Foley R, Hollywood D, Lawler M. Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease. Endocalc Relat Cancer 2004; 11: 477–488.
6. Davoodpour P, Landström M, Welsh M. Reduced tumor growth in vivo and increased c-Abl activity in PC3 prostate cancer cells overexpressing the Shb adapter protein. BMC Cancer 2007; 7: 161.
7. Welsh M, Mares J., Karlsson T, Lavergne C, Breant B, Cleasson-Welsh L. Shb is ubiquitously expressed Src homology 2 protein. Oncogene 1994; 9: 19–27.
8. Welsh M, Songyang Z, Frantz JD, Trub T, Reedquist KA, Karlsson T, Miyazaki M, Cantley LC, Band H, Shoelson SE. Stimulation through the T cell receptor leads to interaction between SHB and several signalling proteins. Oncogene 1998; 16: 891–901.
9. Yulug IG, Hillermann R, Fisher EM. Th e Shb adaptor protein maps to human chromosome
9. Genomics 1994; 24: 615–617.
10. Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Cleasson-Welsh M. Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins. Oncogene 1995; 10: 1475–1483.
11. Lowe SW, Cepero E, Evan G. Instrinsic tumour supression. Nature 2004; 432: 307–315.
12. Igney FH, Kramer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2002; 2: 277–288.
13. Kumar S, Mishra N, Raina D, Saxena S, Kufe D. Abrogation of the cell death response to oxidative stress by the c-Abl tyrosine kinase inhibitor STI571. Mol Pharmacol 2003; 63: 276–282.
14. Hagerkvist R, Mokhtari D, Lindholm C, Farnebo F, Mostoslavsky G, Mulligan RC, Welsh N, Welsh M. Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli. Exp Cell Res 2007; 313: 284–291.
15. Lingge L, Holmquist K, Cross M, Welsh M. Role of the Src homology 2 domain-containing protein Shb in murine brain endothelial cell proliferation and diff erentiation. Cell Growth Differ 2002; 13(3): 141–148.
16. Funa NS, Reddy K, Bhandarkar S, Kurenova EV, Yang L, Cance WG, Welsh M, Arbiser JL. Shb gene knockdown increases the susceptibility of SVR endothelial tumor cells to apoptotic stimuli in vitro and in vivo. J Invest Dermatol 2008; 128: 710–716.
17. Funa NS, Kriz V, Zang G., Calounova G, Akerblom B, Mares J, Larsson E., Sun Y, Betsholtz C, Welch M. Dysfunctional microvasculature as a consequence of Shb gene inactivation causes impaired tumor growth. Cancer Res 2009; 69(5): 2141–2148.
18. Standy TA, Caldwell M, McNeal JE, Nolley R, Hemenex M, Dosna J. Th e prostate specifi c antigen era in the United States is over for prostate cancer: Chat happyend in the last 20 years?
J Urology 2004; 172(4 Pt 1): 1297–1301.
Labels
Paediatric urologist Nephrology UrologyArticle was published in
Czech Urology
2012 Issue 1
Most read in this issue
- Complications associated with indwelling urethral catheter aft er major joint arthroplasty in men
- How safe is active surveillance strategy of small renal masses?
- Use of neuromodulation in the treatment of lower urinary tract dysfunction
- Bilateral adrenalectomy – in patients with Cushing’s syndrome due to ectopic secretion of ACTH