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  • Oncogenomics
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pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis

Oncogene volume 22, pages 6959–6969 (2003)Cite this article

Abstract

The retinoblastoma gene family consisting of RB/p105, p107, and RB2/p130 cooperate to regulate cell-cycle progression through the G1 phase of the cell cycle. Previous data demonstrated an independent role for the reduction or loss of pRb2/p130 expression in the formation and/or progression of lung carcinoma. Rb2/p130 is mutated in a human cell line of lung small cell carcinoma as well as in primary lung tumors. To identify potential pRb2/p130 target genes in an unbiased manner, we have utilized an adenovirus-mediated expression system of pRb2/p130 in a non-small lung cancer cell line to identify specific genes that are regulated by pRb2/p130. Using oligonucleotide arrays, a number of Rb2/p130 downregulated genes were identified and their regulation was confirmed by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) and Western blot analysis. As a result, 40 genes showed greater than 2.0-fold modification in their expression level after the RB2/p130 viral transduction. In conclusion, coupling adenoviral overexpression with microarray and semiquantitative RT–PCR analyses proved to be a versatile strategy for identifying pRb2/p130 target genes and for better understanding the expression profiles of these genes. Our results may also contribute to identifying novel therapeutic biomarkers in lung carcinoma.

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References

  • Baldi A, Esposito V, De Luca A, Fu Y, Meoli I, Giordano GG, Caputi M, Baldi F and Giordano A . (1997). Clin. Cancer Res., 3, 1691–1697.

  • Baldi A, Esposito V, De Luca A, Howard CM, Mazzarella G, Baldi F, Caputi M and Giordano A . (1996). Clin. Cancer Res., 2, 1239–1245.

  • Bhattacharya N, Wang Z, Davitt C, McKenzie IF, Xing PX and Magnuson NS . (2002). Chromosoma, 111, 80–95.

  • Caputi M, Groeger AM, Esposito V, Dean C, De Luca A, Pacilio C, Muller MR, Giordano GG, Baldi F, Wolner E and Giordano A . (1999). Am. J. Respir. Cell. Mol. Biol., 20, 746–750.

  • Claudio PP, De Luca A, Howard CM, Baldi A, Firpo EJ, Koff A, Paggi MG and Giordano A . (1996). Cancer Res., 56, 2003–2008.

  • Claudio PP, Fratta L, Farina F, Howard CM, Stassi G, Numata S, Pacilio C, Davis A, Lavitrano M, Volpe M, Wilson JM, Trimarco B, Giordano A and Condorelli G . (1999). Circ. Res., 85, 1032–1039.

  • Claudio PP, Howard CM, Baldi A, De Luca A, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B and Giordano A . (1994). Cancer Res., 54, 5556–5560.

  • Claudio PP, Howard CM, Pacilio C, Cinti C, Romano G, Minimo C, Maraldi NM, Minna JD, Gelbert L, Leoncini L, Tosi GM, Hicheli P, Caputi M, Giordano GG and Giordano A . (2000). Cancer Res., 60, 372–382.

  • Cunningham MD, Cleaveland J and Nadler SG . (2003). Biochem. Biophys. Res. Commun., 300, 403–407.

  • Davis AR, Meyers K and Wilson JM . (1998). Gene Therapy, 5, 1148–1152.

  • Fambrough D, McClure K, Kazlauskas A and Lander ES . (1999). Cell, 97, 727–741.

  • Fathi Z, Way JW, Corjay MH, Viallet J, Sausville EA and Battey JF . (1996). J. Cell Biochem., 24 (Suppl.), 237–246.

  • Forgacs E, Zochbauer-Muller S, Olah E and Minna JD . (2001). Pathol. Oncol. Res., 7, 6–13.

  • Gillett C, Fantl V, Smith R, Fisher C, Bartek J, Dickson C, Barnes D and Peters G . (1994). Cancer Res., 54, 1812–1817.

  • Glover DM, Hagan IM and Tavares AA . (1998). Genes Dev., 12, 3777–3787.

  • Gorgoulis VG, Zacharatos P, Mariatos G, Kotsinas A, Bouda M, Kletsas D, Asimacopoulos PJ, Agnantis N, Kittas C and Papavassiliou AG . (2002). J. Pathol., 198, 142–156.

  • Greenberg AK, Basu S, Hu J, Yie TA, Tchou-Wong KM, Rom WN and Lee TC . (2002). Am. J. Respir. Cell Mol. Biol., 26, 558–564.

  • Greenlee RT, Hill-Harmon MB, Murray T and Thun M . (2001). CA Cancer J. Clin., 51, 15–36.

  • Helin K, Holm K, Niebuhr A, Eiberg H, Tommerup N, Hougaard S, Poulsen HS, Spang-Thomsen M and Norgaard P . (1997). Proc. Natl. Acad. Sci. USA, 94, 6933–6938.

  • Hibi K, Liu Q, Beaudry GA, Madden SL, Westra WH, Wehage SL, Yang SC, Heitmiller RF, Bertelsen AH, Sidransky D and Jen J . (1998). Cancer Res., 58, 5690–5694.

  • Hoyt Jr RF, Sorokin SP, McDowell EM and McNelly NA . (1993). Anat. Rec., 236, 15–22 discussion 22–24.

  • Jiang Y, Cui L, Yie TA, Rom WN, Cheng H and Tchou-Wong KM . (2001). Oncogene, 20, 2254–2263.

  • Kawai T, Suzuki M, Kono S, Shinomiya N, Rokutanda M, Takagi K, Ogata T and Tamai S . (1994). Cancer, 74, 2468–2475.

  • Keyomarsi K and Pardee AB . (1993). Proc. Natl. Acad. Sci. USA, 90, 1112–1116.

  • Lane S, Farlie P and Watson R . (1997). Oncogene, 14, 2445–2453.

  • Lyon J, Robinson C and Watson R . (1994). Crit. Rev. Oncog., 5, 373–388.

  • Malinin NL, Boldin MP, Kovalenko AV and Wallach D . (1997). Nature, 385, 540–544.

  • Markey MP, Angus SP, Strobeck MW, Williams SL, Gunawardena RW, Aronow BJ and Knudsen ES . (2002). Cancer Res., 62, 6587–6597.

  • Marshall CJ . (1994). Curr. Opin. Genet Dev., 4, 82–89.

  • Masuda A and Takahashi T . (2002). Oncogene, 21, 6884–6897.

  • Mathews MB, Bernstein RM, Franza Jr BR and Garrels JI . (1984). Nature, 309, 374–376.

  • Milligan SA and Nopajaroonsri C . (2001). Anticancer Res., 21, 39–44.

  • Minimo C, Bibbo M, Claudio PP, De Luca A and Giordano A . (1999). Pathol. Res. Pract., 195, 67–70.

  • Motokura T and Arnold A . (1993). Biochim. Biophys. Acta, 1155, 63–78.

  • Mukhopadhyay T, Roth JA and Maxwell SA . (1995). Oncogene, 11, 999–1003.

  • Muller D, Millon R, Velten M, Bronner G, Jung G, Engelmann A, Flesch H, Eber M, Methlin G and Abecassis J . (1997). Eur. J. Cancer, 33, 2203–2210.

  • Nigg EA . (1998). Curr. Opin. Cell Biol., 10, 776–783.

  • Ohman Forslund K and Nordqvist K . (2001). Exp. Cell Res., 265, 185–194.

  • Paggi MG, Baldi A, Bonetto F and Giordano A . (1996). J. Cell Biochem., 62, 418–430.

  • Ramakrishna G, Perella C, Birely L, Diwan BA, Fornwald LW and Anderson LM . (2002). Toxicol. Appl. Pharmacol., 179, 21–34.

  • Raschella G, Negroni A, Pucci S, Amendola R, Valeri S and Calabretta B . (1996). Exp. Cell Res., 222, 395–399.

  • Raschella G, Tanno B, Bonetto F, Amendola R, Battista T, De Luca A, Giordano A and Paggi MG . (1997). J. Cell Biochem., 67, 297–303.

  • Reissmann PT, Koga H, Figlin RA, Holmes EC and Slamon DJ . (1999). J. Cancer Res. Clin. Oncol., 125, 61–70.

  • Rozengurt E . (1988). Ann. NY Acad. Sci., 547, 277–292.

  • Sala A, Casella I, Bellon T, Calabretta B, Watson RJ and Peschle C . (1996). J. Biol. Chem., 271, 9363–9367.

  • Sala A, Kundu M, Casella I, Engelhard A, Calabretta B, Grasso L, Paggi MG, Giordano A, Watson RJ, Khalili K and Peschle C . (1997). Proc. Natl. Acad. Sci. USA, 94, 532–536.

  • Schaeffer HJ and Weber MJ . (1999). Mol. Cell. Biol., 19, 2435–2444.

  • Schauer IE, Siriwardana S, Langan TA and Sclafani RA . (1994). Proc. Natl. Acad. Sci. USA, 91, 7827–7831.

  • Siegfried JM, Krishnamachary N, Gaither Davis A, Gubish C, Hunt JD and Shriver SP . (1999). Pulm. Pharmacol. Ther., 12, 291–302.

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

  • Sugita M, Geraci M, Gao B, Powell RL, Hirsch FR, Johnson G, Lapadat R, Gabrielson E, Bremnes R, Bunn PA and Franklin WA . (2002). Cancer Res., 62, 3971–3979.

  • Teng DH, Chen Y, Lian L, Ha PC, Tavtigian SV and Wong AK . (2001). Genomics, 74, 352–364.

  • Van den Eynde BJ and van der Bruggen P . (1997). Curr. Opin. Immunol., 9, 684–693.

  • Volm M and Koomagi R . (2000). Br. J. Cancer, 82, 1747–1754.

  • Wiest JS, Franklin WA, Drabkin H, Gemmill R, Sidransky D and Anderson MW . (1997). J. Cell Biochem., 28–29 (Suppl.), 64–73.

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

  • Yano T, Yano Y, Nagashima Y, Yuasa M, Yajima S, Horikawa S, Hagiwara K, Kishimoto M, Ichikawa T and Otani S . (1999). Life Sci., 64, 229–236.

  • Yuan J, Horlin A, Hock B, Stutte HJ, Rubsamen-Waigmann H and Strebhardt K . (1997). Am. J. Pathol., 150, 1165–1172.

  • Yuan J, Kramer A, Eckerdt F, Kaufmann M and Strebhardt K . (2002). Cancer Res., 62, 4186–4190.

  • Zwicker J, Liu N, Engeland K, Lucibello FC and Muller R . (1996). Science, 271, 1595–1597.

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Acknowledgements

This work was supported by NIH grants and the Sbarro Health Organization to AG. G.R. acknowledges the Ph.D. program: “Diagnostic, quantitative, and molecular pathology” of the University of Siena, Italy.

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Authors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, 19122, PA, USA

    Giuseppe Russo, Pier Paolo Claudio, Peter Stiegler, Marcella Macaluso & Antonio Giordano

  2. Institute of Human Pathology and Oncology, University of Siena, Italy

    Giuseppe Russo

  3. Dipartimento di Scienze Odontostomatologiche e Maxillo-Facciali, Universita' di Napoli ‘Federico II’, Italy

    Pier Paolo Claudio

  4. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, 19107, PA, USA

    Yan Fu

  5. Jefferson Medical College, KCI Room 376, 1020 Locust Street, Philadelphia, PA 19107, Pennsylvania, USA

    Zailin Yu

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  1. Giuseppe Russo
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Correspondence to Antonio Giordano.

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Russo, G., Claudio, P., Fu, Y. et al. pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis. Oncogene 22, 6959–6969 (2003). https://doi.org/10.1038/sj.onc.1206866

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