DOI QR코드

DOI QR Code

Integrin-linked Kinase Functions as a Tumor Promoter in Bladder Transitional Cell Carcinoma

  • Wang, De-Lin (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Lan, Jian-Hua (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Chen, Liang (Department of Urology, the Kunming Children's Hospital) ;
  • Huang, Biao (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Li, Zeng (Department of Urology, the Cancer institute of Sichuan) ;
  • Zhao, Xiu-Min (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Ma, Qiang (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Sheng, Xia (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Li, Wen-Bin (Department of Urology, the First Affiliated Hospital of Chongqing Medical University) ;
  • Tang, Wei-Xue (Chongqing Key Laboratory of Neurology)
  • Published : 2012.06.30

Abstract

The aim of this study was to elucidate the role of the integrin-linked kinase (ILK) gene in development of human bladder transitional cell carcinoma (BTCC). Expression of ILK protein and ILK mRNA in 56 cases of human BTCC tissue and in 30 cases of adjacent normal bladder tissue was detected by immunohistochemistry S-P and reverse transcription polymerase chain reaction (RT-PCR), respectively. Four specific miRNA RNAi vectors targeting human ILK were synthesized and transfected into BIU-87 cells by liposome to obtain stable expression cell strains. The influence of ILK on proliferation of BTCC was detected by MTT, FCM on athymic mouse tumorigenesis. The positive rate of ILK protein in BTCC tissue (53.6%) was much higher than adjacent normal bladder tissue (10.0%) (p<0.05). Similarly, expression of ILK mRNA in BTCC tissue ($0.540{\pm}0.083$) was significantly higher than in adjacent normal bladder tissue ($0.492{\pm}0.070$) (p<0.05). MTT showed that the proliferation ability of miRNA-ILK transfected group was clearly decreased (p<0.05), the cell cycle being arrested in G0/G1-S, an tumorigenesis in vivo was also significantly reduced (p<0.05). ILK gene transcription and protein expression may be involved in the development of BTCC, so that ILK might be the new marker for early diagnosis and the new target for gene treatment.

Keywords

Bladder neoplasms;integrin-linked kinase;miRNA;RNAi;stable transfection

References

  1. Ahmed N, Riley C, Oliva K, et al (2003). Integrin-linked kinase expression increases with ovarian tumour grade and is sustained by peritoneal tumour fluid. J Pathol, 201, 229-37. https://doi.org/10.1002/path.1441
  2. Attwell S, Roskelley C, Dedhar S (2000). The integrin-linked kinase (ILK) suppresses anoikis. Oncogene, 19, 3811-5. https://doi.org/10.1038/sj.onc.1203711
  3. Fuchs BC, Fujii T, Dorfman JD, et al (2008). Epithelial-tomesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res, 68, 2391-9. https://doi.org/10.1158/0008-5472.CAN-07-2460
  4. Giancotti FG, Ruoslahti E (1999). Integrin signaling. Science, 285, 1028-32. https://doi.org/10.1126/science.285.5430.1028
  5. Graff JR, Deddens JA, Konicek BW, et al (2001). Integrin-linked kinase expression increases with prostate tumor grade. Clin Cancer Res, 7, 1987-91.
  6. Gu R, Bai J, Ling L, et al (2012). Increased expression of integrin-linked kinase improves cardiac function and decreases mortality in dilated cardiomyopathy model of rats. PLoS One, 7, e31279. https://doi.org/10.1371/journal.pone.0031279
  7. Ito R, Oue N, Zhu X, et al (2003). Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma. Virchows Arch, 442, 118-23.
  8. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  9. Kaiser R, Friedrich D, Chavakis E, Böhm M, Friedrich EB (2012). Effect of hypoxia on integrin-mediated adhesion of endothelial progenitor cells. J Cell Mol Med. doi: 10.1111/j.1582-4934.2012.01553.x.
  10. Kieffer N, Schmitz M, Plançon S, et al (2005). ILK as a potential marker gene to ascertain specific adenocarcinoma cell mRNA isolation from frozen prostate biopsy tissue sections. Int J Oncol, 26, 1549-58.
  11. Koul D, Shen R, Bergh S, et al (2005). Targeting integrin-linked kinase inhibits Akt signaling pathways and decreases tumor progression of human glioblastoma. Mol Cancer Ther, 4, 1681-8. https://doi.org/10.1158/1535-7163.MCT-05-0258
  12. Li Q, Xu T, He PY, Hao YC, Wang XF (2010). Effect of integrinlinked kinase on the growth of prostate cancer in nude mice. Beijing Da Xue Xue Bao, 42, 374-80.
  13. Liu Q, Xiao L, Yuan D, Shi X, Li P (2012). Silencing of the integrin-linked kinase gene induces the apoptosis in ovarian carcinoma. J Recept Signal Transduct Res, 32, 120-7. https://doi.org/10.3109/10799893.2012.660534
  14. Marotta A, Parhar K, Owen D, Dedhar S, Salh B (2003). Characterisation of integrin-linked kinase signalling in sporadic human colon cancer. Br J Cancer, 88, 1755-62. https://doi.org/10.1038/sj.bjc.6600939
  15. McDonald PC, Fielding AB, Dedhar S (2008). Integrin-linked kinase--essential roles in physiology and cancer biology. J Cell Sci, 121, 3121-32. https://doi.org/10.1242/jcs.017996
  16. Mello CC, Conte D Jr (2004). Revealing the world of RNA interference. Nature, 431, 338-42. https://doi.org/10.1038/nature02872
  17. Naska S, Park KJ, Hannigan GE, et al (2006). An essential role for the integrin-linked kinase -glycogen synthase kinase-3 beta pathway during dendrite initiation and growth. J Neurosci, 26, 13344-56. https://doi.org/10.1523/JNEUROSCI.4462-06.2006
  18. Oloumi A, McPhee T, Dedhar S (2004). Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim Biophys Acta, 1691, 1-15. https://doi.org/10.1016/j.bbamcr.2003.12.002
  19. Persad S, Attwell S, Gray V, et al (2000). Inhibition of integrinlinked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTENmutant prostate cancer cells. Proc Natl Acad Sci USA, 97, 3207-12. https://doi.org/10.1073/pnas.97.7.3207
  20. Takanami I (2005). Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer. BMC Cancer, 5, 1-7. https://doi.org/10.1186/1471-2407-5-1
  21. Tan C, Cruet-Hennequart S, Troussard A, et al (2004). Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell, 5, 79-90. https://doi.org/10.1016/S1535-6108(03)00281-2
  22. Tang G (2005). siRNA and miRNA: an insight into RISCs. Trends Biochem Sci, 30, 106-14. https://doi.org/10.1016/j.tibs.2004.12.007
  23. Zhang X, Li Y, Huang Q, et al (2003). Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase. Clin Cancer Res, 9, 1155-60.
  24. Zhao G, Guo LL, Xu JY, et al (2011). Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth. World J Gastroenterol, 17, 3487-96. https://doi.org/10.3748/wjg.v17.i30.3487

Cited by

  1. Bladder Cancer Biomarkers: Review and Update vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2395
  2. YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells vol.12, pp.4, 2015, https://doi.org/10.3892/mmr.2015.4005