Identification of maspin and s100p as novel hypomethylation targets in pancreatic cancer using global gene expression profiling

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Identification of maspin and s100p as novel hypomethylation targets in pancreatic cancer using global gene expression profiling"


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ABSTRACT DNA hypomethylation is one of the major epigenetic alterations in human cancers. We have previously shown that genes identified as hypomethylated in pancreatic cancer are expressed


in pancreatic cancer cell lines, but not in normal pancreatic ductal epithelium and can be reexpressed in nonexpressing cells using ‘epigenetic modifying agents’ such as DNA


methyltransferase inhibitors. To identify additional targets for aberrant hypomethylation in pancreatic cancer, we used oligonucleotide microarrays to screen for genes that displayed


expression patterns associated with hypomethylation. This analysis identified a substantial number of candidates including previously reported hypomethylated genes. A subset of eight genes


were selected for further methylation analysis, and two cancer-related genes, _maspin_ and _S100P_, were found to be aberrantly hypomethylated in a large fraction of pancreatic cancer cell


lines and primary pancreatic carcinomas. Combined treatment with 5-aza-2′-deoxycytidie and trichostatin A resulted in synergistic induction of _maspin_ and _S100P_ mRNA in MiaPaCa2 cells


where both genes were methylated. Furthermore, there was an inverse correlation between methylation and mRNA expression level for _maspin_ and _S100P_ in a large panel of pancreatic cancer


cell lines. We also found a significant difference in the methylation patterns of _maspin_ and two previously identified hypomethylated genes (_trefoil factor 2_ and _lipocalin 2_) between


pancreatic and breast cancer cell lines, suggesting cancer-type specificity for some hypomethylation patterns. Thus, our present results confirm that DNA hypomethylation is a frequent


epigenetic event in pancreatic cancer, and suggest that gene expression profiling may help to identify potential targets affected by this epigenetic alteration. Access through your


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Open access 23 June 2020 ABBREVIATIONS * 5Aza-dC: 5-aza-2′-deoxycytidine * TSA: trichostatin A * MSP: methylation-specific PCR * RT–PCR: reverse transcription–PCR REFERENCES * Bachman KE,


Park BH, Rhee I, Rajagopalan H, Herman JG, Baylin SB, Kinzler KW and Vogelstein B . (2003). _Cancer Cell_, 3, 89–95. * Bird A . (2002). _Genes Dev._, 16, 6–21. * Chen RZ, Pettersson U, Beard


C, Jackson-Grusby L and Jaenisch R . (1998). _Nature (London)_, 395, 89–93. * Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P,


Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK and Plass C . (2000). _Nat. Genet._,


24, 132–138. * De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F and Boon T . (1996). _Proc. Natl. Acad. Sci. USA_, 93, 7149–7153. * Diaz VM, Planaguma J, Thomson TM, Reventos J and


Paciucci R . (2002). _Gastroenterology_, 122, 806–819. * Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S and Pelicci PG .


(2002). _Science_, 295, 1079–1082. * Domann FE, Rice JC, Hendrix MJ and Futscher BW . (2000). _Int. J. Cancer_, 85, 805–810. * Ehrlich M . (2002). _Oncogene_, 21, 5400–5413. * Esteller M,


Corn PG, Baylin SB and Herman JG . (2001). _Cancer Res._, 61, 3225–3229. * Feinberg AP and Vogelstein B . (1983). _Nature (London)_, 301, 89–92. * Fukushima N, Sato N, Sahin F, Su GH, Hruban


RH and Goggins M . (2003). _Br. J. Cancer_, 89, 338–343. * Fukushima N, Sato N, Ueki T, Rosty C, Walter KM, Wilentz RE, Yeo CJ, Hruban RH and Goggins M . (2002). _Am. J. Pathol._, 160,


1573–1581. * Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H and Domann FE . (2002). _Nat. Genet_, 31, 175–179. * Gardiner-Garden M and Frommer M . (1987). _J. Mol. Biol._,


196, 261–282. * Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H and Jaenisch R . (2003). _Science_, 300, 489–492. * Goggins M, Kern SE, Offerhaus JA and


Hruban RH . (1999). _Ann. Oncol._, 10, 4–8. * Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X and Russo J . (2000). _Int. J. Oncol._, 16, 231–240. * Guo Y, Pakneshan P,


Gladu J, Slack A, Szyf M and Rabbani SA . (2002). _J. Biol. Chem._, 277, 41571–41579. * Gupta A, Godwin AK, Vanderveer L, Lu A and Liu J . (2003). _Cancer Res._, 63, 664–673. * Herman JG,


Graff JR, Myohanen S, Nelkin BD and Baylin SB . (1996). _Proc. Natl. Acad. Sci. USA_, 93, 9821–9826. * Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato


N, Parker A, Ashfaq R, Jaffee E, Ryu B, Jones J, Eshleman JR, Yeo CJ, Cameron JL, Kern SE, Hruban RH, Brown PO and Goggins M . (2003). _Am. J. Pathol._, 162, 1151–1162. * Iacobuzio-Donahue


CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R, Walter K, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M and Hruban RH . (2002). _Am. J. Pathol._, 160, 1239–1249.


* Jones PA and Baylin SB . (2002). _Nat. Rev. Genet._, 3, 415–428. * Koltzscher M, Neumann C, Konig S and Gerke V . (2003). _Mol. Biol. Cell_, 14, 2372–2384. * Liang G, Gonzales FA, Jones


PA, Orntoft TF and Thykjaer T . (2002). _Cancer Res._, 62, 961–966. * Logsdon CD, Simeone DM, Binkley C, Arumugam T, Greenson JK, Giordano TJ, Misek DE and Hanash S . (2003). _Cancer Res._,


63, 2649–2657. * Maass N, Biallek M, Rosel F, Schem C, Ohike N, Zhang M, Jonat W and Nagasaki K . (2002). _Biochem. Biophys. Res. Commun._, 297, 125–128. * Maass N, Hojo T, Ueding M, Luttges


J, Kloppel G, Jonat W and Nagasaki K . (2001). _Clin. Cancer Res._, 7, 812–817. * Mackay A, Jones C, Dexter T, Silva RL, Bulmer K, Jones A, Simpson P, Harris RA, Jat PS, Neville AM, Reis


LF, Lakhani SR and O'Hare MJ . (2003). _Oncogene_, 22, 2680–2688. * Matsubayashi H, Sato N, Fukushima N, Yeo CJ, Walter KM, Brune K, Sahin F, Hruban RH and Goggins M . (2003). _Clin.


Cancer Res._, 9, 1446–1452. * Mousses S, Bubendorf L, Wagner U, Hostetter G, Kononen J, Cornelison R, Goldberger N, Elkahloun AG, Willi N, Koivisto P, Ferhle W, Raffeld M, Sauter G and


Kallioniemi OP . (2002). _Cancer Res._, 62, 1256–1260. * Oshiro MM, Watts GS, Wozniak RJ, Junk DJ, Munoz-Rodriguez JL, Domann FE and Futscher BW . (2003). _Oncogene_, 22, 3624–3634. *


Pakneshan P, Xing RH and Rabbani SA . (2003). _FASEB J._, 17, 1081–1088. * Rosty C, Ueki T, Argani P, Jansen M, Yeo CJ, Cameron JL, Hruban RH and Goggins M . (2002). _Am. J. Pathol._, 160,


45–50. * Ryu B, Jones J, Blades NJ, Parmigiani G, Hollingsworth MA, Hruban RH and Kern SE. . (2002). _Cancer Res._, 62, 819–826. * Sato N, Fukushima N, Maehara N, Matsubayashi H, Koopmann J,


Su GH, Hruban RH and Goggins M . (2003a). _Oncogene_, 22, 5021–5030. * Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, Hruban RH and Goggins M . (2003b). _Cancer Res._,


63, 3735–3742. * Sato N, Maehara N, Su GH and Goggins M . (2003c). _J. Natl. Cancer Inst._, 95, 327–330. * Sato N, Maitra A, Fukushima N, van Heek NT, Matsubayashi H, Iacobuzio-Donahue CA,


Rosty C and Goggins M . (2003d). _Cancer Res._, 63, 4158–4166. * Sheng S, Carey J, Seftor EA, Dias L, Hendrix MJ and Sager R . (1996). _Proc. Natl. Acad. Sci. USA_, 93, 11669–11674. *


Smiraglia DJ, Rush LJ, Fruhwald MC, Dai Z, Held WA, Costello JF, Lang JC, Eng C, Li B, Wright FA, Caligiuri MA and Plass C . (2001). _Hum. Mol. Genet._, 10, 1413–1419. * Soengas MS,


Capodieci P, Polsky D, Mora J, Esteller M, Opitz-Araya X, McCombie R, Herman JG, Gerald WL, Lazebnik YA, Cordon-Cardo C and Lowe SW . (2001). _Nature (London)_, 409, 207–211. * Sood AK,


Fletcher MS, Gruman LM, Coffin JE, Jabbari S, Khalkhali-Ellis Z, Arbour N, Seftor EA and Hendrix MJ . (2002). _Clin. Cancer Res._, 8, 2924–2932. * Suzuki H, Gabrielson E, Chen W, Anbazhagan


R, van Engeland M, Weijenberg MP, Herman JG and Baylin SB . (2002). _Nat. Genet._, 31, 141–149. * Takai D and Jones PA . (2002). _Proc. Natl. Acad. Sci. USA_, 99, 3740–3745. * Ueki T, Toyota


M, Skinner H, Walter KM, Yeo CJ, Issa JP, Hruban RH and Goggins M . (2001). _Cancer Res._, 61, 8540–8546. * Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH and Goggins M . (2000).


_Cancer Res._, 60, 1835–1839. * Yao X, Hu JF, Daniels M, Shiran H, Zhou X, Yan H, Lu H, Zeng Z, Wang Q, Li T and Hoffman AR . (2003). _J. Clin. Invest._, 111, 265–273. * Zhu WG, Dai Z, Ding


H, Srinivasan K, Hall J, Duan W, Villalona-Calero MA, Plass C and Otterson GA . (2001). _Oncogene_, 20, 7787–7796. * Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K,


Seftor E and Sager R . (1994). _Science_, 263, 526–529. * Zou Z, Gao C, Nagaich AK, Connell T, Saito S, Moul JW, Seth P, Appella E and Srivastava S . (2000). _J. Biol. Chem._, 275,


6051–6054. Download references ACKNOWLEDGEMENTS This work was supported by the SPORE in Gastrointestinal Malignancies (CA62924), the Grant CA90709, and the Michael Rolfe Foundation. We thank


Dr Scott E Kern (The Johns Hopkins Medical Institutions, Baltimore, MD, USA) for providing the DNA samples from pancreatic cancer xenografts and Dr Mieke Schutte (University Hospital


Rotterdam, The Netherlands) for providing DNA samples from breast cancer cell lines. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pathology, The Johns Hopkins Medical


Institutions, Baltimore, MD, USA Norihiro Sato, Noriyoshi Fukushima, Hiroyuki Matsubayashi & Michael Goggins * Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore,


MD, USA Michael Goggins * Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA Michael Goggins Authors * Norihiro Sato View author publications You can also


search for this author inPubMed Google Scholar * Noriyoshi Fukushima View author publications You can also search for this author inPubMed Google Scholar * Hiroyuki Matsubayashi View author


publications You can also search for this author inPubMed Google Scholar * Michael Goggins View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING


AUTHOR Correspondence to Michael Goggins. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sato, N., Fukushima, N., Matsubayashi, H. _et al._


Identification of _maspin_ and _S100P_ as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. _Oncogene_ 23, 1531–1538 (2004).


https://doi.org/10.1038/sj.onc.1207269 Download citation * Received: 18 August 2003 * Revised: 10 October 2003 * Accepted: 10 October 2003 * Published: 29 December 2003 * Issue Date: 26


February 2004 * DOI: https://doi.org/10.1038/sj.onc.1207269 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a


shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * hypomethylation * maspin *


_SERPINB5_ * _S100P_ * microarray


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