Skip to main content
Log in

Transcription factors NF-kB, HIF-1, HIF-2, growth factor VEGF, VEGFR2 and carboanhydrase IX mRNA and protein level in the development of kidney cancer metastasis

  • Molecular Cell Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Here, we have investigated the participation of nuclear factors NF-kB, HIF-1 and HIF-2, VEGF, VEGFR2, and carboanhydrase IX in clear-cell renal cancer. We have determined the expression and protein level of transcription factors, VEGF, VEGFR2, and carboanhydrase IX in tumor and normal tissues of 30 patients with kidney cancer. The Real-Time PCR and ELISA were used in the study. The low levels of HIF-1 mRNA expression associated with high levels of HIF-1 protein were also associated with metastasis. The expression levels of VEGF, VEGFR2, and their protein levels are increased in primary tumors of patients with disseminated kidney cancer compared to nonmetastatic cancer. No correlation was revealed between the content of mRNA and encoded proteins in the kidney cancer tissues. The changes in the ratios of mRNA levels and the respective proteins (HIF-1α, HIF-2, NF-kB, VEGF, VEGFR2, and carboanhydrase IX) may contribute to kidney- cancer metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Badewiijns M.M., van Vlodrop I.J., Vermeulen P.B., Soetekouw P.M., van Engeland M., de Bruine A.P 2010. VHL and HIF signalling in renal cell carcinogenesis. J. Pathol. 221(2), 125–138.

    Article  Google Scholar 

  2. Spirina L.V., Kondakova I.V., Usynin E.A., Vintizenko S.I 2008. regulation of angiogenesis in malignant neoplasms of the kidney and urinary bladder. Sib. Onkol. Zh. 4, 65–70.

    Google Scholar 

  3. Yurmazov Z.A., Usynin E.A., Spirina L.V., Kondakova I.V., Slonimskaya E.M 2015. Prognostic significance of the expression of transcription factors, VEGF growth factor, its receptor, m-TOR protein kinase, and intracellular proteinase activities in patients with disseminated kidney cancer. Sib. Onkol. Zh. 5, 44–50.

    Google Scholar 

  4. Spirina V.L., Usynin E.A., Kondakova I.V., Yurmazov Z.A., Slonimskaya E.M 2015. Molecular markers of kidney cancer progression, association with efficiency of pazopanib therapy. J. Biomed. Sci. Engin. 8, 756–766.

    Article  Google Scholar 

  5. Badalian G., Derecskei K., Szendroi A., Szendroi M., Tímár J 2007. EGFR and VEGFR2 protein expressions in bone metastases of clear cell renal cancer. Anticancer Res. 27(2), 889–894.

    CAS  PubMed  Google Scholar 

  6. Sourbier C., Srivastava G., Ghosh M.C, Ghosh S., Yang Y., Gupta G., Degraff W., Krishna M.C., Mitchell J.B., Rouault T.A., Linehan W.M 2012. Targeting HIF2a translation with Tempol in VHL-deficient clear cell renal cell carcinoma. Oncotarget. 3(11), 1472–1482.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sakamoto T., Seiki M 2009. Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1. J. Biol. Chem. 284(44), 30350–30359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Driessen A., Landyut W., Pastorekova S., Moons J., Goethals L., Haustermans K., Nafteus P., PenninckzF., Geboes K., Lerut T., Ectors N 2006. Expression of carbonic anhydrase IX (CA IX), a hypoxiarelated protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas. Ann. Surg. 243(3), 334–340.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Fan Y., Dutta J., Gupta N., Fan G., Celinas C 2008. Regulation of programmed cell death by NF-kappaB and its role in tumorigenesis and therapy. Adv. Exp. Med. Biol. 315, 223–250.

    Article  Google Scholar 

  10. Greenbaum D., Colangelo C., Williams K., Gerstein M 2003. Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol. 4, 117.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Guo Y., Xiao P., Lei S., Deng F., Xiao G.G., Liu Y., Chen X., Li L., Wu S., Chen Y., Jiang H., Tan L., Xie J., Zhu X., Liang S., Deng H 2008. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim. Biophys. Sin. (Shanghai). 40(5), 426-436.

    Article  CAS  PubMed  Google Scholar 

  12. Hao J.F., Ren K.M., Bai J.X., Wang S.N., Shao B., Cao N., Li X 2014. Identification of potential biomarkers for clear cell renal cell carcinoma based on microRNA–mRNA pathway relationships. J. Cancer Res. Therap. 10, 167–183.

    Article  Google Scholar 

  13. Vasselli J.R., Shih J.H., Iyengar S.R., Maranchie J., Riss J., Worrell R., Torres-Cabala C., Tabios R., Mariotti A., Stearman R., Merino M., Walther M.M., Simon R., Klausner R.D., Linehan W.M 2003. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor. Proc. Natl. Acad. Sci. U. S. A. 100, 6958–6963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lidgren A., Bergh A., Grankvist K., Lindh G., Ljungberg B 2008. Hypoxia-inducible factor-1a mRNA and protein levels in renal cell carcinoma. J. Cancer Mol. 4(5), 153–157.

    CAS  Google Scholar 

  15. Biswas S., Troy H., Leek R., Chung Y.L., Li J.L., Raval R.R., Turley H., Gatter K., Pezzella F., Griffiths J.R., Stubbs M., Harris A.L 2010. Effects of HIF-1alpha and HIF2alpha on growth and metabolism of clear-cell renal cell carcinoma 786-0 xenografts. J. Oncol. 1155, 757908–757915.

    Google Scholar 

  16. Tian Q., Stepaniants S.B., Mao M., Weng L., Feetham M.C., Doyle M.J., Yi E.C., Dai H., Thorsson V., Eng J., Goodlett D., Berger J.P., Gunter B., Linseley P.S., Stoughton R.B., et al 2004. Integrated genomic and proteomic analyses of gene expression in mammalian cells. Mol. Cell. Proteomics. 3(10), 960–969.

    Article  CAS  PubMed  Google Scholar 

  17. Schwanhausser B., Busse D., Li N., Dittmar G., Schuchhardt J., Wolf J., Chen W., Selbach M 2011. Global quantification of mammalian gene expression control. Nature. 473(7347), 337–342.

    Article  PubMed  Google Scholar 

  18. Fu L., Wang G., Shevchuk M.M., Nanus D.M., Gudas L.J 2013. Activation of HIF2a in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis. Cancer Res. 73(9), 2916–2925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Maier T., Guell M., Serrano L 2009. Correlation of mRNA and protein in complex biological samples. FEBS Lett. 583(24), 3966–3973.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. V. Spirina.

Additional information

Original Russian Text © L.V. Spirina, Y.A. Usynin, Z.A. Yurmazov, E.M. Slonimskaya, E.S. Kolegova, I.V. Kondakova, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 2, pp. 372–377.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spirina, L.V., Usynin, Y.A., Yurmazov, Z.A. et al. Transcription factors NF-kB, HIF-1, HIF-2, growth factor VEGF, VEGFR2 and carboanhydrase IX mRNA and protein level in the development of kidney cancer metastasis. Mol Biol 51, 328–332 (2017). https://doi.org/10.1134/S0026893317020194

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893317020194

Keywords

Navigation