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Transcription of TIMP3, DAPK1, and AKR1B10 in squamous-cell lung cancer

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Abstract

Lung cancer is among the most common neoplasms in Russia, the United States, and in Western Europe and is accompanied by changes in the functional activity of many genes. The transcription levels of TIMP3, DAPK1, and AKR1B10 were compared for normal and tumor lung tissues of patients with squamous-cell cancer (SCC) by RT-PCR. A substantial increase in AKR1B10 transcription level was observed in 80% of the tumors. The transcription levels of TIMP3 and DAPK1 were significantly decreased in 76 and 72% of the tumors, respectively. The results implicated the genes in carcinogenesis in SCC, AKR1B10 acting as a potential oncogene, and TIMP3 and DAPK1 acting as potential tumor suppressor genes. It was assumed that dramatic changes in their transcription levels could be used for early diagnosis of SCC.

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References

  1. Jemal A., Siegel R., Ward E., Murray T., Xu J., Smigal C., Thun M.J. 2006. Cancer statistics, 2006. CA Cancer J. Clin. 56, 6–30.

    Article  Google Scholar 

  2. Zaridze D.G. 2004. Epidemiology and etiology of malignant tumors. In: Kantserogenez (Carcinogenesis). Ed. Zaridze D.G. Moscow: Meditsina.

    Google Scholar 

  3. Dammann R., Strunnikova M., Schagdarsurengin U., Rastetter M., Papritz M., Hattenhorst U.E., Hofmann H.S., Silber R.E., Burdach S., Hansen G. 2005. CpG island methylation and expression of tumour-associated genes in lung carcinoma. Eur. J. Cancer. 41, 1223–1236.

    Article  CAS  PubMed  Google Scholar 

  4. Toyooka S., Toyooka K.O., Miyajima K., Reddy J.L., Toyota M., Sathyanarayana U.G., Padar A., Tockman M.S., Lam S., Shivapurkar N., Gazdar A.F. 2003. Epigenetic down-regulation of death-associated protein kinase in lung cancers. Clin. Cancer Res. 9, 3034–3041.

    CAS  PubMed  Google Scholar 

  5. Fukumoto S., Yamauchi N., Moriguchi H., Hippo Y., Watanabe A., Shibahara J., Taniguchi H., Ishikawa S., Ito H., Yamamoto S., Iwanari H., Hironaka M., Ishikawa Y., Niki T., Sohara Y., Kodama T., Nishimura M., Fukayama M., Dosaka-Akita H., Aburatani H. 2005. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin. Cancer Res. 11, 1776–1785.

    Article  CAS  PubMed  Google Scholar 

  6. Penning T.M. 2005. AKR1B10: A new diagnostic marker of non-small cell lung carcinoma in smokers. Clin. Cancer Res. 11, 1687–1690.

    Article  CAS  PubMed  Google Scholar 

  7. Drynda A., Quax P.H., Neumann M., van der Laan W.H., Pap G., Drynda S., Meinecke I., Kekow J., Neumann W., Huizinga T.W., Naumann M., Konig W., Pap T. 2005. Gene transfer of tissue inhibitor of metalloproteinases-3 reverses the inhibitory effects of TNF-alpha on Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. J. Immunol. 174, 6524–6531.

    CAS  PubMed  Google Scholar 

  8. Han X., Zhang H., Jia M., Han G., Jiang W. 2004. Expression of TIMP-3 gene by construction of a eukaryotic cell expression vector and its role in reduction of metastasis in a human breast cancer cell line. Cell Mol. Immunol. 13, 8–10.

    Google Scholar 

  9. Apte S.S., Olsen B.R., Murphy G. 1995. The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J. Biol. Chem. 270, 14,313–14,318.

    CAS  Google Scholar 

  10. Brueckl W.M., Grombach J., Wein A., Ruckert S., Porzner M., Dietmaier W., Rummele P., Croner R.S., Boxberger F., Kirchner T., Hohenberger W., Hahn E.G., Jung A. 2005. Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI). Cancer Lett. 223, 137–142.

    Article  CAS  PubMed  Google Scholar 

  11. Cheng Y.W., Shawber C., Notterman D., Paty P., Barany F. 2006. Multiplexed profiling of candidate genes for CpG island methylation status using a flexible PCR/LDR/Universal Array assay. Genome Res. 16, 282–289.

    Article  CAS  PubMed  Google Scholar 

  12. Kettunen E., Anttila S., Seppanen J.K., Karjalainen A., Edgren H., Lindstrom I., Salovaara R., Nissen A.M., Salo J., Mattson K., Hollmen J., Knuutila S., Wikman H. 2004. Differentially expressed genes in non-small cell lung cancer: Expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet. Cytogenet. 149, 98–106.

    Article  CAS  PubMed  Google Scholar 

  13. Riddick A.C., Shukla C.J., Pennington C.J., Bass R., Nuttall R.K., Hogan A., Sethia K.K., Ellis V., Collins A.T., Maitland N.J., Ball R.Y., Edwards D.R. 2005. Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br. J. Cancer. 92, 2171–2180.

    Article  CAS  PubMed  Google Scholar 

  14. Vazquez-Ortiz G., Pina-Sanchez P., Vazquez K., Duenas A., Taja L., Mendoza P., Garcia J.A., Salcedo M. 2005. Overexpression of cathepsin F, matrix metalloproteinases 11 and 12 in cervical cancer. BMC Cancer. 5, 68.

    Article  PubMed  CAS  Google Scholar 

  15. Wikman H., Kettunen E., Seppanen J.K., Karjalainen A., Hollmen J., Anttila S., Knuutila S. 2002. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene. 21, 5804–5813.

    Article  CAS  PubMed  Google Scholar 

  16. Inbal B., Cohen O., Polak-Charcon S., Kopolovic J., Vadai E., Eisenbach L., Kimchi A. 1997. DAP kinase links the control of apoptosis to metastasis. Nature. 390, 180–184.

    Article  CAS  PubMed  Google Scholar 

  17. Kogel D., Prehn J.H., Scheidtmann K.H. 2001. The DAP kinase family of pro-apoptotic proteins: Novel players in the apoptotic game. Bioessays. 23, 352–358.

    Article  CAS  PubMed  Google Scholar 

  18. Kwong J., Lo K.W., To K.F., Teo P.M., Johnson P.J., Huang D.P. 2002. Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin. Cancer Res. 8, 131–137.

    CAS  PubMed  Google Scholar 

  19. Simpson D.J., Clayton R.N., Farrell W.E. 2002. Preferential loss of Death Associated Protein kinase expression in invasive pituitary tumours is associated with either CpG island methylation or homozygous deletion. Oncogene. 21, 1217–1224.

    Article  CAS  PubMed  Google Scholar 

  20. Cao D., Fan S.T., Chung S.S. 1998. Identification and characterization of a novel human aldose reductase-like gene. J. Biol. Chem. 273, 11,429–11,435.

    CAS  Google Scholar 

  21. Hyndman D., Bauman D.R., Heredia V.V., Penning T.M. 2003. The aldo-keto reductase superfamily homepage. Chem. Biol. Interact. 143–144, 621–631.

    Article  PubMed  CAS  Google Scholar 

  22. Hyndman D.J., Flynn T.G. 1998. Sequence and expression levels in human tissues of a new member of the aldo-keto reductase family. Biochim. Biophys. Acta. 1399, 198–202.

    CAS  PubMed  Google Scholar 

  23. Martin H.J., Breyer-Pfaff U., Wsol V., Venz S., Block S., Maser E. 2006. Purification and characterization of AKR1B10 from human liver: Role in carbonyl reduction of xenobiotics. Drug Metab. Dispos. 34, 464–470.

    Article  CAS  PubMed  Google Scholar 

  24. Scuric Z., Stain S.C., Anderson W.F., Hwang J.J. 1998. New member of aldose reductase family proteins over-expressed in human hepatocellular carcinoma. Hepatology. 27, 943–950.

    Article  CAS  PubMed  Google Scholar 

  25. Sambrook J., Fritsch E.F., Maniatis T. 1989. Molecular Cloning: A Laboratory Manual. 2nd ed. Cold Spring Harbor, New York: Cold Spring Harbor Lab. Press.

    Google Scholar 

  26. Chomczynski P., Mackey K. 1995. Modification of the TRI reagent procedure for isolation of RNA from polysaccharide-and proteoglycan-rich sources. Biotechniques. 19, 942–945.

    CAS  PubMed  Google Scholar 

  27. 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, 892–897.

    CAS  PubMed  Google Scholar 

  28. Belinsky S.A., Klinge D.M., Dekker J.D., Smith M.W., Bocklage T.J., Gilliland F.D., Crowell R.E., Karp D.D., Stidley C.A., Picchi M.A. 2005. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin. Cancer Res. 11, 6505–6511.

    Article  CAS  PubMed  Google Scholar 

  29. Kang S., Kim J.W., Kang G.H., Lee S., Park N.H., Song Y.S., Park S.Y., Kang S.B., Lee H.P. 2006. Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma, and endometrial adenocarcinoma. Int. J. Cancer. 118, 2168–2171.

    Article  CAS  PubMed  Google Scholar 

  30. Russo A.L., Thiagalingam A., Pan H., Califano J., Cheng K.H., Ponte J.F., Chinnappan D., Nemani P., Sidransky D., Thiagalingam S. 2005. Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin. Cancer Res. 11, 2466–2470.

    Article  CAS  PubMed  Google Scholar 

  31. Safar A.M., Spencer H. 3rd, Su X., Coffey M., Cooney C.A., Ratnasinghe L.D., Hutchins L.F., Fan C.Y. 2005. Methylation profiling of archived non-small cell lung cancer: A promising prognostic system. Clin. Cancer Res. 11, 4400–4405.

    Article  CAS  PubMed  Google Scholar 

  32. Esteller M., Corn P.G., Baylin S.B., Herman J.G. 2001. A gene hypermethylation profile of human cancer. Cancer Res. 61, 3225–3229.

    CAS  PubMed  Google Scholar 

  33. Kim Y.T., Park S.J., Lee S.H., Kang H.J., Hahn S., Kang C.H., Sung S.W., Kim J.H. 2005. Prognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lung. J. Thorac. Cardiovasc. Surg. 130, 1378.

    Article  CAS  PubMed  Google Scholar 

  34. Lu C., Soria J.C., Tang X., Xu X.C., Wang L., Mao L., Lotan R., Kemp B., Bekele B.N., Feng L., Hong W.K., Khuri F.R. 2004. Prognostic factors in resected stage I non-small-cell lung cancer: A multivariate analysis of six molecular markers. J. Clin. Oncol. 22, 4575–4583.

    Article  PubMed  Google Scholar 

  35. Soria J.C., Rodriguez M., Liu D.D., Lee J.J., Hong W.K., Mao L. 2002. Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers. Cancer Res. 62, 351–355.

    CAS  PubMed  Google Scholar 

  36. Yanagawa N., Tamura G., Oizumi H., Takahashi N., Shimazaki Y., Motoyama T. 2003. Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers. Cancer Sci. 94, 589–592.

    Article  CAS  PubMed  Google Scholar 

  37. Girard L., Zochbauer-Muller S., Virmani A.K., Gazdar A.F., Minna J.D. 2000. Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res. 60, 4894–4906.

    CAS  PubMed  Google Scholar 

  38. Pastor A., Menendez R., Cremades M.J., Pastor V., Llopis R., Aznar J. 1997. Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: A Bayesian analysis. Eur. Respir. J. 10, 603–609.

    CAS  PubMed  Google Scholar 

  39. Thun M.J., Henley S.J., Calle E.E. 2002. Tobacco use and cancer: An epidemiologic perspective for genetics. Oncogene. 21, 7307–7325.

    Article  CAS  PubMed  Google Scholar 

  40. Powell C.A., Spira A., Derti A., DeLisi C., Liu G., Borczuk A., Busch S., Sahasrabudhe S., Chen Y., Sugarbaker D., Bueno R., Richards W.G., Brody J.S. 2003. Gene expression in lung adenocarcinomas of smokers and nonsmokers. Am. J. Respir. Cell Mol. Biol. 29, 157–162.

    Article  CAS  PubMed  Google Scholar 

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Original Russian Text © T.D. Mashkova, N.Yu. Oparina, O.L. Zinov’eva, E.S. Kropotova, V.I. Dubovaya, A.B. Poltaraus, M.V. Fridman, E.P. Kopantsev, T.V. Vinogradova, M.V. Zinov’eva, K.K. Laktionov, O.T. Kasymova, I.B. Zborovskaya, E.D. Sverdlov, L.L. Kisselev, 2006, published in Molekulyarnaya Biologiya, 2006, Vol. 40, No. 6, pp. 1047–1054.

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Mashkova, T.D., Oparina, N.Y., Zinov’eva, O.L. et al. Transcription of TIMP3, DAPK1, and AKR1B10 in squamous-cell lung cancer. Mol Biol 40, 945–951 (2006). https://doi.org/10.1134/S0026893306060148

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  • DOI: https://doi.org/10.1134/S0026893306060148

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