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  • Original Paper
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Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array

Abstract

No clear patterns in molecular changes underlying the malignant processes in lung cancer of different histological types have been found so far. To identify critical genes in lung cancer progression we compared the expression profile of cancer related genes in 14 pulmonary adenocarcinoma patients with normal lung tissue by using the cDNA array technique. Principal component analyses (PCA) and permutation test were used to detect the differentially expressed genes. The expression profiles of 10 genes were confirmed by semi-quantitative real-time RT–PCR. In tumour samples, as compared to normal lung tissue, the up-regulated genes included such known tumour markers as CCNB1, PLK, tenascin, KRT8, KRT19 and TOP2A. The down-regulated genes included caveolin 1 and 2, and TIMP3. We also describe, for the first time, down-regulation of the interesting SOCS2 and 3, DOC2 and gravin. We show that silencing of SOCS2 is not caused by methylation of exon 1 of the gene. In conclusion, by using the cDNA array technique we were able to reveal marked differences in the gene expression level between normal lung and tumour tissue and find possible new tumour markers for pulmonary adenocarcinoma.

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References

  • Aalto Y, El-Rifai W, Vilpo L, Ollila J, Nagy B, Vihinen M, Vilpo J, Knuutila S . 2001 Leukemia 15: 1721–1728

  • Anbazhagan R, Tihan T, Bornman DM, Johnston JC, Saltz JH, Weigering A, Piantadosi S, Gabrielson E . 1999 Cancer Res. 59: 5119–5122

  • Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, Sallan SE, Lander ES, Golub TR, Korsmeyer SJ . 2002 Nat. Genet. 30: 41–47

  • Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K . 2000 Cancer Epidemiol. Biomarkers Prev. 9: 3–28

  • Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M . 2001 Proc. Natl. Acad. Sci. USA 98: 13790–13795

  • Björkqvist AM, Husgafvel-Pursiainen K, Anttila S, Karjalainen A, Tammilehto L, Mattson K, Vainio H, Knuutila S . 1998a Genes Chromosomes Cancer 22: 79–82

  • Björkqvist AM, Tammilehto L, Nordling S, Nurminen M, Anttila S, Mattson K, Knuutila S . 1998b Br J Cancer 77: 260–269

  • Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM . 1998 J. Biol. Chem. 273: 25680–25685

  • Bornslaeger EA, Corcoran CM, Stappenbeck TS, Green KJ . 1996 J. Cell. Biol. 134: 985–1001

  • Caligo MA, Cipollini G, Fiore L, Calvo S, Basolo F, Collecchi P, Ciardiello F, Pepe S, Petrini M, Bevilacqua G . 1995 Int. J. Cancer 60: 837–842

  • Chen JJ, Peck K, Hong TM, Yang SC, Sher YP, Shih JY, Wu R, Cheng JL, Roffler SR, Wu CW, Yang PC . 2001 Cancer Res. 61: 5223–5230

  • Chu W, Burns DK, Swerlick RA, Presky DH . 1995 J. Biol. Chem. 270: 10236–10245

  • Cilley RE, Zgleszewski SE, Chinoy MR . 2000 J. Pediatr. Surg. 35: 113–118 discussion 119

  • Diviani D, Scott JD . 2001 J. Cell. Sci. 114: 1431–1437

  • Dohmoto K, Hojo S, Fujita J, Ueda Y, Bandoh S, Yamaji Y, Ohtsuki Y, Dobashi N, Takahara J . 2000 Lung Cancer 30: 55–63

  • Dohr O, Sinning R, Vogel C, Munzel P, Abel J . 1997 Mol. Pharmacol. 51: 703–710

  • Engelman JA, Zhang XL, Galbiati F, Lisanti MP . 1998 FEBS Lett. 429: 330–336

  • Everett AD, Stoops TD, McNamara CA . 2001 J. Biol. Chem. 31: 31

  • Fassina G, Ferrari N, Brigati C, Benelli R, Santi L, Noonan DM, Albini A . 2000 Clin. Exp. Metastasis 18: 111–120

  • Feliciello A, Gottesman ME, Avvedimento EV . 2001 J. Mol. Biol. 308: 99–114

  • Fong KM, Kida Y, Zimmerman PV, Smith PJ . 1996 Clin. Cancer Res. 2: 1369–1372

  • Fulop V, Colitti CV, Genest D, Berkowitz RS, Yiu GK, Ng SW, Szepesi J, Mok SC . 1998 Oncogene 17: 419–424

  • Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I . 2001 Proc. Natl. Acad. Sci. USA 98: 13784–13789

  • Gemma A, Takenaka K, Hosoya Y, Matuda K, Seike M, Kurimoto F, Ono Y, Uematsu K, Takeda Y, Hibino S, Yoshimura A, Shibuya M, Kudoh S . 2001 Eur. J. Cancer 37: 1554–1561

  • Hand D, Mannila H, Smyth P . 2001 Adaptive Computation and Machine Learning Series: Principles of Data Mining Boston: MIT Press 425 pp

    Google Scholar 

  • Hautamäki RD, Kobayashi DK, Senior RM, Shapiro SD . 1997 Science 277: 2002–2004

  • Hefferan TE, Subramaniam M, Khosla S, Riggs BL, Spelsberg TC . 2000 J. Cell. Biochem. 78: 380–390

  • Hellmann GM, Fields WR, Doolittle DJ . 2001 Toxicol. Sci. 61: 154–163

  • Hilsenbeck SG, Friedrichs WE, Schiff R, O'Connell P, Hansen RK, Osborne CK, Fuqua SA . 1999 J. Natl. Cancer Inst. 91: 453–459

  • Hocevar BA, Smine A, Xu XX, Howe PH . 2001 EMBO J. 20: 2789–2801

  • Holtrich U, Wolf G, Brauninger A, Karn T, Bohme B, Rubsamen-Waigmann H, Strebhardt K . 1994 Proc. Natl. Acad. Sci. USA 91: 1736–1740

  • Huang Y, Friess H, Kleeff J, Esposito I, Zhu Z, Liu S, Mok SC, Zimmermann A, Buchler MW . 2001 Lab. Invest. 81: 863–873

  • Husgafvel-Pursiainen K, Hackman P, Ridanpää M, Anttila S, Karjalainen A, Partanen T, Taikina-Aho O, Heikkilä L, Vainio H . 1993 Int. J. Cancer 53: 250–256

  • Jaques G, Noll K, Wegmann B, Witten S, Kogan E, Radulescu RT, Havemann K . 1997 Endocrinology 138: 1767–1770

  • Kamimura A, Kamachi M, Nishihira J, Ogura S, Isobe H, Dosaka-Akita H, Ogata A, Shindoh M, Ohbuchi T, Kawakami Y . 2000 Cancer 89: 334–341

  • Kang SH, Choi HH, Kim SG, Jong HS, Kim NK, Kim SJ, Bang YJ . 2000 Int. J. Cancer 86: 632–635

  • Karameris A, Panagou P, Tsilalis T, Bouros D . 1997 Am. J. Respir. Crit. Care Med. 156: 1930–1936

  • Kazmierczak B, Meyer-Bolte K, Tran KH, Wockel W, Breightman I, Rosigkeit J, Bartnitzke S, Bullerdiek J . 1999 Genes Chromosomes Cancer 26: 125–133

  • Kellner U, Rudolph P, Parwaresch R . 2000 Onkologie 23: 424–430

  • Kettunen E, Nissén AM, Ollikainen T, Taavitsainen M, Tapper J, Mattson K, Linnainmaa K, Knuutila S, El-Rifai W . 2001 Int. J. Cancer 91: 492–496

  • Keohavong P, DeMichele MA, Melacrinos AC, Landreneau RJ, Weyant RJ, Siegfried JM . 1996 Clin. Cancer Res. 2: 411–418

  • Kim Y, Ratziu V, Choi SG, Lalazar A, Theiss G, Dang Q, Kim SJ, Friedman SL . 1998 J. Biol. Chem. 273: 33750–33758

  • Kishimoto T, Kikutani H . 2001 Nat. Genet. 28: 4–5

  • Kojima S, Hayashi S, Shimokado K, Suzuki Y, Shimada J, Crippa MP, Friedman SL . 2000 Blood 95: 1309–1316

  • Krebs DL, Hilton DJ . 2001 Stem Cells 19: 378–387

  • Kusagawa H, Onoda K, Namikawa S, Yada I, Okada A, Yoshida T, Sakakura T . 1998 Br. J. Cancer 77: 98–102

  • Laronga C, Yang HY, Neal C, Lee MH . 2000 J. Biol. Chem. 275: 23106–23112

  • Lee IH, Chang SI, Okada K, Baba H, Shiku H . 1997 Mol. Cells 7: 589–593

  • Matikainen T, Perez GI, Jurisicova A, Pru JK, Schlezinger JJ, Ryu HY, Laine J, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH, Tilly JL . 2001 Nat. Genet. 28: 355–360

  • Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T . 1997 Biochem. Biophys. Res. Commun. 237: 79–83

  • Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, Ng SW, Baldini A, Colitti CV, Rock CO, Berkowitz RS . 1998 Oncogene 16: 2381–2387

  • Nakanishi K, Hashizume S, Kato M, Honjoh T, Setoguchi Y, Yasumoto K . 1997 Hum. Antibodies 8: 189–194

  • Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM, Birembaut P . 1997 Int. J. Cancer 72: 556–564

  • Nhung NV, Mirejovsky P, Mirejovsky T, Melinova L . 1999 Cesk. Patol. 35: 80–84

  • Nishihira J . 1998 Int. J. Mol. Med. 2: 17–28

  • Pendleton N, Occleston NL, Walshaw MJ, Littler JA, Jack CI, Myskow MW, Green JA . 1994 Eur. J. Cancer 1: 93–96

  • Pines J, Hunter T . 1992 Ciba Found. Symp. 170: 187–196

  • Racine C, Belanger M, Hirabayashi H, Boucher M, Chakir J, Couet J . 1999 Biochem. Biophys. Res. Commun. 255: 580–586

  • Ratziu V, Lalazar A, Wong L, Dang Q, Collins C, Shaulian E, Jensen S, Friedman SL . 1998 Proc. Natl. Acad. Sci. USA 95: 9500–9505

  • Razani B, Lisanti MP . 2001 Am. J. Physiol. Cell Physiol. 281: C1241–C1250

  • Reeves R, Nissen MS . 1995 Prog. Cell Cycle Res. 1: 339–349

  • Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C, Chilvers ER, Dransfield I, Donnelly SC, Strieter R, Haslett C . 1999 Nat. Med. 5: 662–668

  • Smith MM . 1991 Curr. Opin. Cell Biol. 3: 429–437

  • Smith MR, Wilson ML, Hamanaka R, Chase D, Kung H, Longo E, Ferris DK . 1997 Biochem. Biophys. Res. Commun. 234: 397–405

  • Soria JC, Jang SJ, Khuri FR, Hassan K, Liu D, Hong WK, Mao L . 2000 Cancer Res. 60: 4000–4004

  • Suzuki H, Itoh F, Toyota M, Kikuchi T, Kakiuchi H, Hinoda Y, Imai K . 2000 Electrophoresis 21: 904–908

  • Tan DF, Huberman JA, Hyland A, Loewen GM, Brooks JS, Beck AF, Todorov IT, Bepler G . 2001 BMC Cancer 1: 6

  • Thomas P, Khokha R, Shepherd FA, Feld R, Tsao MS . 2000 J. Pathol. 190: 150–156

  • Toyoshima-Morimoto F, Taniguchi E, Shinya N, Iwamatsu A, Nishida E . 2001 Nature 410: 215–220

  • Tseng CP, Ely BD, Pong RC, Wang Z, Zhou J, Hsieh JT . 1999 J. Biol. Chem. 274: 31981–31986

  • Tuder RM, Yeager ME, Geraci M, Golpon HA, Voelkel NF . 2001 Eur. Respir. J. 17: 1065–1069

  • Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, Goggins M . 2000 Cancer Res. 60: 1835–1839

  • Wang T, Hopkins D, Schmidt C, Silva S, Houghton R, Takita H, Repasky E, Reed SG . 2000 Oncogene 19: 1519–1528

  • Wikman H, Risch A, Klimek F, Schmezer P, Spiegelhalder B, Dienemann H, Kayser K, Schulz V, Drings P, Bartsch H . 2000 Int. J. Cancer 88: 932–937

  • Wilkinson MG, Millar JB . 2000 FASEB J. 14: 2147–2157

  • Wilson MJ, Lindquist JA, Trowsdale J . 2000 Immunol. Res. 22: 21–42

  • Wolf G, Elez R, Doermer A, Holtrich U, Ackermann H, Stutte HJ, Altmannsberger HM, Rubsamen-Waigmann H, Strebhardt K . 1997 Oncogene 14: 543–549

  • Wolf M, El-Rifai W, Tarkkanen M, Kononen J, Serra M, Eriksen EF, Elomaa I, Kallioniemi A, Kallioniemi OP, Knuutila S . 2000 Cancer Genet. Cytogenet. 123: 128–132

  • Xia W, Unger P, Miller L, Nelson J, Gelman IH . 2001 Cancer Res. 61: 5644–5651

  • Xiao S, Lux ML, Reeves R, Hudson TJ, Fletcher JA . 1997 Am. J. Pathol. 150: 901–910

  • Ylisirniö S, Höyhtyä M, Mäkitaro R, Pääkkö P, Risteli J, Kinnula VL, Turpeenniemi-Hujanen T, Jukkola A . 2001 Clin. Cancer Res. 7: 1633–1637

  • Yu H, Rohan T . 2000 J. Natl. Cancer Inst. 92: 1472–1489

  • Zochbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD . 2001 Cancer Res. 61: 249–255

  • Zhou BS, Tsai P, Ker R, Tsai J, Ho R, Yu J, Shih J, Yen Y . 1998 Clin. Exp. Metastasis 16: 43–49

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Acknowledgements

We are grateful to Päivi Tuominen and Anna Kannio for their excellent technical assistance. JK Seppänen and J Hollmén wish to thank Dr Heikki Mannila for many helpful discussions. This work was supported by grants from K Albin Johanssons Sitftelse and the Finnish Cancer Foundation.

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Correspondence to Sakari Knuutila.

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Wikman, H., Kettunen, E., Seppänen, J. et al. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 21, 5804–5813 (2002). https://doi.org/10.1038/sj.onc.1205726

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