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.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
Greenbaum D., Colangelo C., Williams K., Gerstein M 2003. Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol. 4, 117.
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.
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.
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.
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.
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.
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.
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.
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.
Maier T., Guell M., Serrano L 2009. Correlation of mRNA and protein in complex biological samples. FEBS Lett. 583(24), 3966–3973.
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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.
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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
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DOI: https://doi.org/10.1134/S0026893317020194