Skip to main content

Advertisement

SpringerLink
Log in

Sequential 5-Aza 2′-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells

  • Original Paper
  • Published:
Oncogene Submit manuscript

Abstract

cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2′-deoxycytidine (DAC)/depsipeptide FK228 (DP) exposure in order to identify translational end points for clinical trials evaluating these agents. In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduction known to diminish the malignant phenotype of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell lines established from thoracic malignancies. Sequential DAC/DP treatment induced TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state. Promoter methylation coincided with loss of TFPI-2 expression in a number of cancer lines. TFPI-2 promoter methylation was observed in one of five pulmonary adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer cells deficient for TFPI-2 expression in the absence of promoter methylation. In these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling and PKC signaling strengthens the preclinical rationale for sequential administration of DNA demethylating agents and HDAC inhibitors in cancer patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of treatment response in individuals receiving sequential DAC/DP infusions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Abe K, Shoji M, Chen J, Bierhaus A, Danave I, Micko C, Casper K, Dillehay DL, Nawroth PP and Rickles FR . (1999). Proc. Natl. Acad. Sci. USA, 96, 8663–8668.

  • Annunziato AT and Hansen JC . (2000). Gene Expr., 9, 37–61.

  • Attwood JT, Yung RL and Richardson BC . (2002). Cell Mol. Life Sci., 59, 241–257.

  • Baker AH, Edwards DR and Murphy G . (2002). J. Cell Sci., 115, 3719–3727.

  • Bender CM, Pao MM and Jones PA . (1998). Cancer Res., 58, 95–101.

  • Brinkmann H, Dahler AL, Popa C, Serewko MM, Parsons PG, Gabrielli BG, Burgess AJ and Saunders NA . (2001). J. Biol. Chem., 276, 22491–22499.

  • Bromberg ME, Sundaram R, Homer RJ, Garen A and Konigsberg WH . (1999). Thromb. Haemost., 82, 88–92.

  • Cameron EE, Bachman KE, Myohanen S, Herman JG and Baylin SB . (1999). Nat. Genet., 21, 103–107.

  • Cervoni N and Szyf M . (2001). J. Biol. Chem., 276, 40778–40787.

  • Chand HS, Du X, Ma D, Inzunza HD, Kamei S, Foster D, Brodie S and Kisiel W . (2004). Blood, 103, 1069–1077.

  • Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Kohler G, Wijermans P, Jones PA and Lubbert M . (2002). Blood, 100, 2957–2964.

  • Detich N, Bovenzi V and Szyf M . (2003). J. Biol. Chem., 278, 27586–27592.

  • Fahrner JA, Eguchi S, Herman JG and Baylin SB . (2002). Cancer Res., 62, 7213–7218.

  • Folkman J . (1996). Nat. Med., 2, 167–168.

  • Han JW, Ahn SH, Kim YK, Bae GU, Yoon JW, Hong S, Lee HY, Lee YW and Lee HW . (2001). J. Biol. Chem., 276, 42084–42090.

  • Herman JG, Graff JR, Myohanen S, Nelkin BD and Baylin SB . (1996). Proc. Natl. Acad. Sci. USA, 93, 9821–9826.

  • Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P and Schonbeck U . (2001). J. Clin. Invest., 107, 1117–1126.

  • Hjortoe GM, Petersen LC, Albrektsen T, Sorensen BB, Norby PL, Mandal SK, Pendurthi UR and Rao LV . (2004). Blood, 103, 3029–3037.

  • Izumi H, Takahashi C, Oh J and Noda M . (2000). FEBS Lett., 481, 31–36.

  • Jin M, Udagawa K, Miyagi E, Nakazawa T, Hirahara F, Yasumitsu H, Miyazaki K, Nagashima Y, Aoki I and Miyagi Y . (2001). Gynecol. Oncol., 83, 325–333.

  • Jones PA and Baylin SB . (2002). Nat. Rev. Genet., 3, 415–428.

  • Juttermann R, Li E and Jaenisch R . (1994). Proc. Natl. Acad. Sci. USA, 91, 11797–11801.

  • Kamei S, Kazama Y, Kuijper JL, Foster DC and Kisiel W . (2001). Biochim. Biophys. Acta, 1517, 430–435.

  • Kast C, Wang M and Whiteway M . (2003). J. Biol. Chem., 278, 6787–6794.

  • Kazama Y, Kamei S, Kuijper JL, Foster DC and Kisiel W . (2000). Thromb. Haemost., 83, 141–147.

  • Kim YB, Ki SW, Yoshida M and Horinouchi S . (2000). J. Antibiot. (Tokyo), 53, 1191–1200.

  • Konduri SD, Osman FA, Rao CN, Srinivas H, Yanamandra N, Tasiou A, Dinh DH, Olivera WC, Gujrati M, Foster DC, Kisiel W, Kouraklis G and Rao JS . (2002). Oncogene, 21, 921–928.

  • Konduri SD, Rao CN, Chandrasekar N, Tasiou A, Mohanam S, Kin Y, Lakka SS, Dinh D, Olivero WC, Gujrati M, Foster DC, Kisiel W and Rao JS . (2001a). Oncogene, 20, 6938–6945.

  • Konduri SD, Srivenugopal KS, Yanamandra N, Dinh DH, Olivero WC, Gujrati M, Foster DC, Kisiel W, Ali-Osman F, Kondraganti S, Lakka SS and Rao JS . (2003a). Oncogene, 22, 4509–4516.

  • Konduri SD, Tasiou A, Chandrasekar N, Nicolson GL and Rao JS . (2000). Clin. Exp. Metastasis, 18, 303–308.

  • Konduri SD, Tasiou A, Chandrasekar N and Rao JS . (2001b). Int. J. Oncol., 18, 127–131.

  • Konduri SD, Yanamandra N, Dinh DH, Olivero WC, Gujrati M, Foster DC, Kisiel W and Rao JS . (2003b). Int. J. Oncol., 22, 1277–1283.

  • Kouzarides T . (1999). Curr. Opin. Genet. Dev., 9, 40–48.

  • Lakka SS, Konduri SD, Mohanam S, Nicolson GL and Rao JS . (2000). Clin. Exp. Metastasis, 18, 239–244.

  • Lehman TA, Bennett WP, Metcalf RA, Welsh JA, Ecker J, Modali RV, Ullrich S, Romano JW, Appella E, Testa JR, Gerwin BI and Harris CC . (1991). Cancer Res., 51, 4090–4096.

  • Liu Y, Stack SM, Lakka SS, Khan AJ, Woodley DT, Rao JS and Rao CN . (1999). Arch. Biochem. Biophys., 370, 112–118.

  • Markl ID, Cheng J, Liang G, Shibata D, Laird PW and Jones PA . (2001). Cancer Res., 61, 5875–5884.

  • Marks PA, Richon VM and Rifkind RA . (2000). J. Natl. Cancer Inst., 92, 1210–1216.

  • Mueller BM, Reisfeld RA, Edgington TS and Ruf W . (1992). Proc. Natl. Acad. Sci. USA, 89, 11832–11836.

  • Mueller BM and Ruf W . (1998). J. Clin. Invest, 101, 1372–1378.

  • Mukhopadhyay T, Tainsky M, Cavender AC and Roth JA . (1991). Cancer Res., 51, 1744–1748.

  • Nakajima H, Kim YB, Terano H, Yoshida M and Horinouchi S . (1998). Exp. Cell Res., 241, 126–133.

  • Neaud V, Hisaka T, Monvoisin A, Bedin C, Balabaud C, Foster DC, Desmouliere A, Kisiel W and Rosenbaum J . (2000). J. Biol. Chem., 275, 35565–35569.

  • Nguyen DM, Schrump WD, Chen GA, Tsai W, Nguyen P, Trepel JB and Schrump DS . (2004). Clin. Cancer Res., 10, 1813–1825.

  • Poulsen LK, Jacobsen N, Sorensen BB, Bergenhem NC, Kelly JD, Foster DC, Thastrup O, Ezban M and Petersen LC . (1998). J. Biol. Chem., 273, 6228–6232.

  • Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W and Woodley DT . (1998). Int. J. Cancer, 76, 749–756.

  • Rao CN, Lakka SS, Kin Y, Konduri SD, Fuller GN, Mohanam S and Rao JS . (2001). Clin. Cancer Res., 7, 570–576.

  • Rao CN, Mohanam S, Puppala A and Rao JS . (1999). Biochem. Biophys. Res. Commun., 255, 94–98.

  • Rao CN, Reddy P, Liu Y, O'Toole E, Reeder D, Foster DC, Kisiel W and Woodley DT . (1996). Biochem. Biophys., 335, 82–92.

  • Rao CN, Reddy P, Reeder DJ, Liu Y, Stack SM, Kisiel W and Woodley DT . (2000). Biochem. Biophys. Res. Commun., 276, 1286–1294.

  • Rao CN, Segawa T, Navari JR, Xu L, Srivastava S, Moul JW and Phillips B . (2003). Int. J. Oncol., 22, 843–848.

  • Rea S, Eisenhaber F, O'Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD and Jenuwein T . (2000). Nature, 406, 593–599.

  • Richon VM, Sandhoff TW, Rifkind RA and Marks PA . (2000). Proc. Natl. Acad. Sci. USA, 97, 10014–10019.

  • Robertson KD . (2001). Oncogene, 20, 3139–3155.

  • Sandor V, Senderowicz A, Mertins S, Sackett D, Sausville E, Blagosklonny MV and Bates SE . (2000). Br. J. Cancer, 83, 817–825.

  • Santini V, Kantarjian HM and Issa JP . (2001). Ann. Intern. Med., 134, 573–586.

  • Sato M, Horio Y, Sekido Y, Minna JD, Shimokata K and Hasegawa Y . (2002). Oncogene, 21, 4822–4829.

  • Shapiro GI, Park JE, Edwards CD, Mao L, Merlo A, Sidransky D, Ewen ME and Rollins BJ . (1995). Cancer Res., 55, 6200–6209.

  • Shinoda E, Yui Y, Hattori R, Tanaka M, Inoue R, Aoyama T, Takimoto Y, Mitsui Y, Miyahara K, Shizuta Y and Sasayama S . (1999). J. Biol. Chem., 274, 5379–5384.

  • Siegbahn A, Johnell M, Rorsman C, Ezban M, Heldin CH and Ronnstrand L . (2000). Blood, 96, 3452–3458.

  • Sorensen BB, Freskgard PO, Nielsen LS, Rao LV, Ezban M and Petersen LC . (1999). J. Biol. Chem., 274, 21349–21354.

  • Sprecher CA, Kisiel W, Mathewes S and Foster DC . (1994). Proc. Natl. Acad. Sci. USA, 91, 3353–3357.

  • Suzuki H, Gabrielson E, Chen W, Anbazhagan R, Van Engeland M, Weijenberg MP, Herman JG and Baylin SB . (2002). Nat. Genet., 31, 141–149.

  • Tasiou A, Konduri SD, Yanamandra N, Dinh DH, Olivero WC, Gujrati M, Obeyesekere M and Rao JS . (2001). Int. J. Oncol., 19, 591–597.

  • Ueki T, Walter KM, Skinner H, Jaffee E, Hruban RH and Goggins M . (2002). Oncogene, 21, 2114–2117.

  • Vairapandi M . (2004). J. Cell Biochem., 91, 572–583.

  • Versteeg HH, Hoedemaeker I, Diks SH, Stam JC, Spaargaren M, van Bergen En Henegouwen PM, van Deventer SJ and Peppelenbosch MP . (2000). J. Biol. Chem., 275, 28750–28756.

  • Vigushin DM and Coombes RC . (2002). Anticancer Drugs, 13, 1–13.

  • Wade PA . (2001). Hum. Mol. Genet., 10, 693–698.

  • Weiser TS, Guo ZS, Ohnmacht GA, Parkhurst ML, Tong-On P, Marincola FM, Fischette MR, Yu X, Chen GA, Hong JA, Stewart JH, Nguyen DM, Rosenberg SA and Schrump DS . (2001a). J. Immunother., 24, 151–161.

  • Weiser TS, Ohnmacht GA, Guo ZS, Fischette MR, Chen GA, Hong JA, Nguyen DM and Schrump DS . (2001b). Ann. Thorac. Surg., 71, 295–301.

  • Wojtukiewicz MZ, Sierko E, Zimnoch L, Kozlowski L and Kisiel W . (2003). Thromb. Haemost., 90, 140–146.

  • Yu X, Guo ZS, Marcu MG, Neckers L, Nguyen DM, Chen GA and Schrump DS . (2002). J. Natl. Cancer Inst., 94, 504–513.

  • Zacharski LR, Memoli VA, Rousseau SM and Kisiel W . (1987). Cancer, 60, 2675–2681.

  • Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA and Marks PA . (2000). Proc. Natl. Acad. Sci. USA, 97, 14329–14333.

  • Zhu WG, Lakshmanan RR, Beal MD and Otterson GA . (2001). Cancer Res., 61, 1327–1333.

Download references

Author information

Authors and Affiliations

  1. Thoracic Oncology Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Federico A Steiner, Julie A Hong, Maria R Fischette, Zong-Sheng Guo, G Aaron Chen, Todd S Weiser, Edmund S Kassis, Dao M Nguyen & David S Schrump

  2. Thoracic Surgery Section, University of Michigan Medical Center, Ann Arbor, MI, USA

    David G Beer

  3. Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Sunmin Lee & Jane B Trepel

Authors
  1. Federico A Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie A Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria R Fischette
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David G Beer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zong-Sheng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Aaron Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Todd S Weiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Edmund S Kassis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dao M Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sunmin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jane B Trepel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. David S Schrump
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David S Schrump.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steiner, F., Hong, J., Fischette, M. et al. Sequential 5-Aza 2′-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells. Oncogene 24, 2386–2397 (2005). https://doi.org/10.1038/sj.onc.1208376

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208376

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation