Abstract
Numerous human cancers are accompanied with the increase of ferritin content in blood serum. Ferritin is composed of light and heavy chains, encoded by FTL and FTH genes, respectively. The analysis of EST database showed that the expression of FTL and FTH genes in lung tumors is decreased compared to normal tissues, and is not altered in renal cancer cells. The alteration of mRNA corresponding to FTL and FTH genes was estimated by real-time PCR in primary lung and kidney tumors. A significant and frequent inhibition of FTL and FTH gene expression (on average by 11 and 9 times, in 83% (33/40) and 73% (11/15) of cases, respectively) was detected in primary squamous lung carcinoma. The expression of these genes was not altered so significantly (by 6 and 3 times, in 58% and 27% of samples) in clear cell renal cell carcinoma. Our work reports for the first time the down-regulation of FTL gene expression at the first stage of lung cancer (10/10), and proposes this gene as a potential oncomarker for early diagnosis. The FTL mRNA content may be quantified by non-competitive hybridization on expression DNA microarrays. The possible causes of a serum ferritin increase in lung squamous cell carcinoma and clear cell renal cell carcinoma are discussed.
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Koorts A.M., Viljoen M. 2007. Ferritin and ferritin isoforms II: Protection against uncontrolled cellular proliferation, oxidative damage and inflammatory processes. Arch. Physiol. Biochem. 113(2), 55–64.
Koorts A.M., Viljoen M. 2007. Ferritin and ferritin isoforms I: Structure-function relationships, synthesis, degradation and secretion. Arch. Physiol. Biochem. 113(1), 30–54.
Zaleska M., Szturmowicz M., Zych J., Remiszewski P., Plodziszewskal M., Szopinski J., Zaleska J., Demkow U., Langfort R., Roszkowska-Sliz B., Roszkowski-Sliz K. 2005. The significance of the serum tumour markers as a prognostic and predictor factors in nonsmall cell lung cancer patients. Pneumonol. Alergol. Pol. 73(3), 270–276.
Mertz J.R., Theil E.C. 1983. Subunit dimers in sheep spleen apoferritin: The effect on iron storage. J. Biol. Chem. 258(19), 11719–11726.
Essen A., Ozen H., Ayhan A., Ergen A., Tasar C., Remzi F. 1991. Serum ferritin: A tumor marker for renal cell carcinoma. J. Urol. 145(6), 1134–1137.
Grail A., Hancock B.W., Harrison P. 1092. Serum ferritin in normal individuals and in patients with malignant lymphoma and chronic renal failure measured with seven different commercial immunoassay techniques. J. Clin. Pathol. 35, 1204–1212.
Milman N., Pedersen L. 2002. The serum ferritin concentration is a significant prognostic indicator of survival in primary lung cancer. Oncol. Rep. 9, 193–198.
Kashyap M.K., Kumar A., Emelianenko N., Kashyap A., Kaushik R., Huang R., Khullar M., Sharma S.K., Singh S.K., Bhargave A.K., Upadhyaya S.K. 2005. Biochemical and molecular markers in renal cell carcinoma: An update and future prospects. Biomarkers. 10(4), 258–294.
Ozen H., Uygur C., Sahin A., Tekgul S., Ergen A., Remzi D. 1995. Clinical significance of serum ferritin in patients with renal cell carcinoma. Urology. 46(4), 494–498.
Miyata Y., Koga S., Nishikido M., Hayashi T., Kanetake H. 2001. Relationship between serum ferritin levels and tumour status in patients with renal cell carcinoma. BJU Int. 88(9), 974–977.
Fracchia A., Ubbiali A., El Bitar O., Pacetti M., Sommariva E., Arreghini M., Longhini E., Bonalumi G.P. 1999. A comparative study on ferritin concentration in serum and bilateral bronchoalveolar lavage fluid of patients with peripheral lung cancer versus control subjects. Oncology. 56(3), 181–188.
Shen C., Hui-Zhao, Wang D., Jiang G., Wang J., Zhang G. 2002. Molecular cloning, identification and analysis of lung squamous cell carcinoma-related genes. Lung Cancer. 38(3), 235–241.
Liu Y., Zhu X., Zhu J., Liao S., Tang Q., Liu K., Guan X., Zhang G., Feng Z. 2007. Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray. Oncol. Rep. 18(4), 943–951.
Sambrook J., Frisch E.F., Maniatis T. 1989. Molecular Cloning. A Laboratory Manual, 2nd ed. Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press.
Zhu Y.Y., Machleder E.M., Chenchik A., Li R., Siebert P.D. 2001. Reverse transcriptase template switching: A SMART approach for full-length cDNA library construction. Biotechniques. 30(4), 892–897.
Liu D.W., Chen S.T., Liu H.P. 2005. Choice of endogenous control for gene expression in non-small cell lung cancer. Eur. Respir. J. 26(6), 1002–1008.
Anedchenko E.A., Kiseleva N.P., Dmitriev A.A., Kisselev F.L., Zabarovsky E.R., Senchenko V.N. 2007. Tumor suppressor gene RBSP3 in cervical carcinoma: Copy number and transcription level. Mol. Biol. 41(1), 86–95.
Glantz S.A. 1994. Primer of Biostatistics, 4th ed. N.Y.: McGraw-Hill Inc.
Orino K., Watanabe K. 2008. Molecular, physiological and clinical aspects of the iron storage protein ferritin. Veterinary J. 178(2), 191–201.
Milman N., Pedersen L.M. 2002. The serum ferritin concentration is a significant prognostic indicator of survival in primary lung cancer. Oncol. Rep. 9(1), 193–198.
Singh K.J., Singh S.K., Suri A., Vijjan V., Goswami A.K., Khullar M. 2005. Serum ferritin in renal cell carcinoma: Effect of tumor size, volume grade, and stage. Indian J. Cancer. 42(4), 197–200.
Kirkali Z., Esen A.A., Kirkali G., Guner G. 1995. Ferritin: A tumor marker expressed by renal cell carcinoma. Eur. Urol. 28(2), 131–134.
Partin A.W., Criley S.R., Steiner M.S., Hsieh K., Simons J.W., Lumadue J., Carter H.B., Marshall F.F. 1995. Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor volume. Urology. 45(2), 211–217.
Kirkali Z., Guzelsoy M., Mungan M.U., Kirkali G., Yorukoglu K. 1999. Serum ferritin as a clinical marker for renal cell carcinoma: Influence of tumor size and volume. Urol. Int. 62(1), 21–25.
Sammarco M.C., Ditch S., Banerjee A., Grabczyk E. 2008. Ferritin L subunits are differentially regulated on a post-transcriptional level. J. Biol. Chem. 283(8), 4578–4587.
An H.J., Kim D.S., Park Y.K., Kim S.K., Choi Y.P., Kang S., Ding B., Cho N.H. 2006. Comparative proteomics of ovarian epithelial tumors. J. Proteome Res. 5(5), 1082–1090.
Wigle D.A., Tsao M., Jurisica I. 2004. Making sense of lung-cancer gene-expression profiles. Genome Biol. 5(2), 309.
Blackhall F.H., Wigle D.A., Jurisica I., Pintilie M., Liu N., Darling G., Johnston M.R., Keshavjee S., Waddell T., Winton T., Shepherd F.A., Tsao M.S. 2004. Validating the prognostic value of marker genes derived from a nonsmall cell lung cancer microarray study. Lung Cancer. 46(2), 197–204.
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Original Russian Text © A.V. Kudriavtseva, E.A. Anedchenko, N.Yu. Oparina, G.S. Krasnov, K.N. Kashkin, A.A. Dmitriev, I.B. Zborovskaya, T.T. Kondratjeva, E.V. Vinogradova, M.V. Zinovyeva, E.P. Kopantsev, V.N. Senchenko, 2009, published in Molekulyarnaya Biologiya, 2009, Vol. 43, No. 6, pp. 1044–1054.
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Kudriavtseva, A.V., Anedchenko, E.A., Oparina, N.Y. et al. Expression of FTL and FTH genes encoding ferritin subunits in lung and renal carcinomas. Mol Biol 43, 972–981 (2009). https://doi.org/10.1134/S0026893309060090
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DOI: https://doi.org/10.1134/S0026893309060090