Skip to main content
Erschienen in: Tumor Biology 5/2010

01.10.2010 | Research Article

Strong expression of HDAC3 correlates with a poor prognosis in patients with adenocarcinoma of the lung

verfasst von: Yoshihiro Minamiya, Takashi Ono, Hajime Saito, Naoko Takahashi, Manabu Ito, Satoru Motoyama, Junichi Ogawa

Erschienen in: Tumor Biology | Ausgabe 5/2010

Einloggen, um Zugang zu erhalten

Abstract

Inhibition of histone deacetylases (HDACs) is a promising new approach to the treatment of lung cancer therapy. The relation between HDAC3 expression and the clinicopathological characteristics of lung cancer is not well understood, however. We therefore addressed this issue in patients with adenocarcinoma of the lung. We used semi-quantitative real-time reverse transcription polymerase chain reaction and immunohistochemical analysis to assess expression of HDAC3 in tumor samples from 94 patients with adenocarcinoma of the lung. We then correlated levels of HDAC3 expression with known clinicopathological factors. The 5-year disease-free survival (5-DFS) rate among patients expressing high levels of HDAC3 was significantly poorer than among those expressing lower levels (P = 0.005; log-rank test). Multivariate Cox proportional hazard analyses revealed male (hazard ratio, 3.88; 95% CI, 1.70-9.39; P = 0.001), nodal metastasis N1 (hazard ratio, 6.39; 95% CI, 1.54-22.7; P = 0.013), N2 (hazard ratio, 6.36; 95% CI, 1.55-33.6; P = 0.009), and HDAC3 (hazard ratio, 3.06; 95% CI, 1.07-7.55; P = 0.037) to be independent factors affecting the 5-DFS rate. Strong tumoral expression of HDAC3 is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.
Literatur
1.
Zurück zum Zitat Karagianni P, Wong J. HDAC3: taking the SMRT-N-CoRrect road to repression. Oncogene. 2007;26:5439–49.CrossRefPubMed Karagianni P, Wong J. HDAC3: taking the SMRT-N-CoRrect road to repression. Oncogene. 2007;26:5439–49.CrossRefPubMed
2.
Zurück zum Zitat Weichert W, Röske A, Niesporek S, et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14:x1669–77.CrossRefPubMed Weichert W, Röske A, Niesporek S, et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14:x1669–77.CrossRefPubMed
3.
Zurück zum Zitat Krusche CA, Wülfing P, Kersting C, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat. 2005;90:15–23.CrossRefPubMed Krusche CA, Wülfing P, Kersting C, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat. 2005;90:15–23.CrossRefPubMed
4.
Zurück zum Zitat Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer. 2004;112:26–32.CrossRefPubMed Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer. 2004;112:26–32.CrossRefPubMed
5.
Zurück zum Zitat Sasaki H, Moriyama S, Nakashima Y, et al. Histone deacetylase 1 mRNA expression in lung cancer. Lung Cancer. 2004;46:171–8.CrossRefPubMed Sasaki H, Moriyama S, Nakashima Y, et al. Histone deacetylase 1 mRNA expression in lung cancer. Lung Cancer. 2004;46:171–8.CrossRefPubMed
6.
Zurück zum Zitat Tan J, Cang S, Ma Y, Petrillo RL, Liu D. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol. 2010;3:5.CrossRefPubMed Tan J, Cang S, Ma Y, Petrillo RL, Liu D. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol. 2010;3:5.CrossRefPubMed
7.
Zurück zum Zitat Siegel D, Hussein M, Belani C, et al. Vorinostat in solid and hematologic malignancies. Journal of Hematology & Oncology. 2009;2:31.CrossRef Siegel D, Hussein M, Belani C, et al. Vorinostat in solid and hematologic malignancies. Journal of Hematology & Oncology. 2009;2:31.CrossRef
8.
Zurück zum Zitat Cang S, Ma Y, Liu D. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. Journal of Hematology & Oncology. 2009;2:22.CrossRef Cang S, Ma Y, Liu D. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. Journal of Hematology & Oncology. 2009;2:22.CrossRef
9.
Zurück zum Zitat Cress WD, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol. 2000;184:1–16.CrossRefPubMed Cress WD, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol. 2000;184:1–16.CrossRefPubMed
10.
Zurück zum Zitat Ramalingam SS, Maitland ML, Frankel P, et al. (2010) Carboplatin and paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J Clin Oncol (in press). Ramalingam SS, Maitland ML, Frankel P, et al. (2010) Carboplatin and paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J Clin Oncol (in press).
11.
Zurück zum Zitat Ramalingam SS, Parise RA, Ramanathan RK, et al. Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res. 2007;13:3605–10.CrossRefPubMed Ramalingam SS, Parise RA, Ramanathan RK, et al. Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res. 2007;13:3605–10.CrossRefPubMed
12.
Zurück zum Zitat Vansteenkiste J, Van Cutsem E, Dumez H, et al. Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Invest New Drugs. 2008;26:483–8.CrossRefPubMed Vansteenkiste J, Van Cutsem E, Dumez H, et al. Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Invest New Drugs. 2008;26:483–8.CrossRefPubMed
13.
Zurück zum Zitat Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008;7:759–68.CrossRefPubMed Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008;7:759–68.CrossRefPubMed
14.
Zurück zum Zitat Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6:38–51.CrossRefPubMed Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6:38–51.CrossRefPubMed
15.
Zurück zum Zitat Sobin L, Wittekind CH, editors. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. p. 99–103. Sobin L, Wittekind CH, editors. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. p. 99–103.
16.
Zurück zum Zitat Bendinelli P, Matteucci E, Maroni P, Desiderio MA. NF-kappaB activation, dependent on acetylation/deacetylation, contributes to HIF-1 activity and migration of bone metastatic breast carcinoma cells. Mol Cancer Res. 2009;7:1328–41.CrossRefPubMed Bendinelli P, Matteucci E, Maroni P, Desiderio MA. NF-kappaB activation, dependent on acetylation/deacetylation, contributes to HIF-1 activity and migration of bone metastatic breast carcinoma cells. Mol Cancer Res. 2009;7:1328–41.CrossRefPubMed
17.
Zurück zum Zitat Lf C, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001;293:1653–7.CrossRef Lf C, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001;293:1653–7.CrossRef
18.
Zurück zum Zitat Grégoire S, Xiao L, Nie J, et al. Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Mol Cell Biol. 2007;27:1280–95.CrossRefPubMed Grégoire S, Xiao L, Nie J, et al. Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Mol Cell Biol. 2007;27:1280–95.CrossRefPubMed
19.
Zurück zum Zitat Hayashi A, Horiuchi A, Kikuchi N, et al. (2010) Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with down-regulation of E-cadherin. Int J Cancer (in press) Hayashi A, Horiuchi A, Kikuchi N, et al. (2010) Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with down-regulation of E-cadherin. Int J Cancer (in press)
20.
Zurück zum Zitat Imre G, Gekeler V, Leja A, Beckers T, Boehm M. Histone deacetylase inhibitors suppress the inducibility of nuclear factor-kappaB by tumor necrosis factor-alpha receptor-1 down-regulation. Cancer Res. 2006;66:5409–18.CrossRefPubMed Imre G, Gekeler V, Leja A, Beckers T, Boehm M. Histone deacetylase inhibitors suppress the inducibility of nuclear factor-kappaB by tumor necrosis factor-alpha receptor-1 down-regulation. Cancer Res. 2006;66:5409–18.CrossRefPubMed
21.
Zurück zum Zitat Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells. Int J Cancer. 2010;126:743–55.CrossRefPubMed Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells. Int J Cancer. 2010;126:743–55.CrossRefPubMed
22.
Zurück zum Zitat Takami Y, Nakayama T. N-terminal region, C-terminal region, nuclear export signal, and deacetylation activity of histone deacetylase-3 are essential for the viability of the DT40 chicken B cell line. J Biol Chem. 2000;275:16191–201.CrossRefPubMed Takami Y, Nakayama T. N-terminal region, C-terminal region, nuclear export signal, and deacetylation activity of histone deacetylase-3 are essential for the viability of the DT40 chicken B cell line. J Biol Chem. 2000;275:16191–201.CrossRefPubMed
23.
Zurück zum Zitat Longworth MS, Laimins LA. Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src. Oncogene. 2006;25:4495–500.CrossRefPubMed Longworth MS, Laimins LA. Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src. Oncogene. 2006;25:4495–500.CrossRefPubMed
24.
Zurück zum Zitat Escaffit F, Vaute O, Chevillard-Briet M, et al. Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression. Mol Cell Biol. 2007;27:554–67.CrossRefPubMed Escaffit F, Vaute O, Chevillard-Briet M, et al. Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression. Mol Cell Biol. 2007;27:554–67.CrossRefPubMed
25.
Zurück zum Zitat Jin KL, Pak JH, Park JY, et al. Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues. J Gynecol Oncol. 2008;19:185–90.CrossRefPubMed Jin KL, Pak JH, Park JY, et al. Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues. J Gynecol Oncol. 2008;19:185–90.CrossRefPubMed
26.
Zurück zum Zitat Selvaggi G, Scagliotti GV. Histologic subtype in NSCLC: does it matter? Oncology. 2009;23:1133–40.PubMed Selvaggi G, Scagliotti GV. Histologic subtype in NSCLC: does it matter? Oncology. 2009;23:1133–40.PubMed
27.
Zurück zum Zitat Chang TH, Szabo E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res. 2002;8:1206–12.PubMed Chang TH, Szabo E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res. 2002;8:1206–12.PubMed
28.
Zurück zum Zitat Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol. 2005;45:495–528.CrossRefPubMed Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol. 2005;45:495–528.CrossRefPubMed
Metadaten
Titel
Strong expression of HDAC3 correlates with a poor prognosis in patients with adenocarcinoma of the lung
verfasst von
Yoshihiro Minamiya
Takashi Ono
Hajime Saito
Naoko Takahashi
Manabu Ito
Satoru Motoyama
Junichi Ogawa
Publikationsdatum
01.10.2010
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2010
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-010-0066-0

Weitere Artikel der Ausgabe 5/2010

Tumor Biology 5/2010 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.