nach oben

Cellular Oncology

Erschienen in:

01.04.2013 | Original Paper

Epigenetic control of HNF-4α in colon carcinoma cells affects MUC4 expression and malignancy

verfasst von: Anna Algamas-Dimantov, Einav Yehuda-Shnaidman, Irena Peri, Betty Schwartz

Erschienen in: Cellular Oncology | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

We previously found that enhanced expression of hepatocyte nuclear factor 4α (HNF-4α) is associated with hyper-proliferation of colon carcinoma cells. Here, the effect of histone deacetylase (HDAC) inhibitors on proliferation and the expression of HNF-4α and its downstream target genes were assessed in HM7, LS174T, HT29 and Caco-2 colon carcinoma cell lines.

Results

HNF-4α expression was found to vary in the different colon carcinoma cell lines tested, being highest in HM7. Additionally, a direct correlation with proliferation was observed. In HM7 cells, the weak HDAC inhibitor butyrate significantly inhibited the transcription of HNF-4α, its downstream target gene MUC4, and genes associated with proliferation, including the proliferating cell nuclear antigen gene PCNA. siRNA-mediated silencing of HNF-4α exerted an effect similar to butyrate on HM7 cell proliferation. The stronger HDAC inhibitor trichostatin A (TSA) exerted an effect similar to that of siRNA-mediated HNF-4α silencing and, concomitantly, inhibited the expression of the transcription factor gene SP1. Also, siRNA-mediated silencing of HDAC3 and HDAC4 reduced HNF-4α expression. Chromatin immunoprecipitation (ChIP) assays revealed that TSA induces hyperacetylation of histones H3 and H4 and, concomitantly, inhibits SP1 binding to the HNF-4α promoter. Subsequent electromobility shift assays supported these latter findings.

Conclusions

HNF-4α transcriptional expression and activity are tightly controlled by epigenetic mechanisms. HDAC inhibitor targeting of HNF-4α may serve as an effective treatment for advanced colon carcinomas, since downstream cancer-associated target genes such as MUC4 are significantly down-regulated by this treatment.

Nur mit Berechtigung zugänglich

F.M. Sladek, Orphan receptor HNF-4 and liver-specific gene expression. Receptor 3, 223–232 (1993)PubMed

A.J. Watt, W.D. Garrison, S.A. Duncan, HNF4: a central regulator of hepatocyte differentiation and function. Hepatology 37, 1249–1253 (2003)PubMedCrossRef

A.L. Cattin, J. Le Beyec, F. Barreau, S. Saint-Just, A. Houllier, F.J. Gonzalez, S. Robine, M. Pincon-Raymond, P. Cardot, M. Lacasa, A. Ribeiro, Hepatocyte nuclear factor 4alpha, a key factor for homeostasis, cell architecture, and barrier function of the adult intestinal epithelium. Mol. Cell. Biol. 29, 6294–6308 (2009)PubMedCrossRef

W.D. Garrison, M.A. Battle, C. Yang, K.H. Kaestner, F.M. Sladek, S.A. Duncan, Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon. Gastroenterology 130, 1207–1220 (2006)PubMedCrossRef

S.A. Duncan, K. Manova, W.S. Chen, P. Hoodless, D.C. Weinstein, R.F. Bachvarova, J.E. Darnell Jr., Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc. Natl. Acad. Sci. U. S. A. 91, 7598–7602 (1994)PubMedCrossRef

B. Schwartz, A. Algamas-Dimantov, R. Hertz, J. Nataf, A. Kerman, I. Peri, J. Bar-Tana, Inhibition of colorectal cancer by targeting hepatocyte nuclear factor-4alpha. Int. J. Cancer 124, 1081–1089 (2009)PubMedCrossRef

A. Algamas-Dimantov, D. Davidovsky, J. Ben-Ari, J.X. Kang, I. Peri, R. Hertz, J. Bar-Tana, B. Schwartz, Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids in mice. J. Lipid Res. 53, 1056–1070 (2012)PubMedCrossRef

J.P. Audie, A. Janin, N. Porchet, M.C. Copin, B. Gosselin, J.P. Aubert, Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization. J. Histochem. Cytochem. 41, 1479–1485 (1993)PubMedCrossRef

A.P. Corfield, D. Carroll, N. Myerscough, C.S. Probert, Mucins in the gastrointestinal tract in health and disease. Front. Biosci. 6, D1321–D1357 (2001)PubMedCrossRef

10.

R.S. Bresalier, B. Schwartz, Y.S. Kim, Q.Y. Duh, H.K. Kleinman, P.M. Sullam, The laminin alpha 1 chain Ile-Lys-Val-Ala-Val (IKVAV)-containing peptide promotes liver colonization by human colon cancer cells. Cancer Res. 55, 2476–2480 (1995)PubMed

11.

C. Shanmugam, N.C. Jhala, V.R. Katkoori, W. Wan, S. Meleth, W.E. Grizzle, U. Manne, Prognostic value of mucin 4 expression in colorectal adenocarcinomas. Cancer 116, 3577–3586 (2010)PubMedCrossRef

12.

N. Jonckheere, A. Vincent, M. Perrais, M.P. Ducourouble, A.K. Male, J.P. Aubert, P. Pigny, K.L. Carraway, J.N. Freund, I.B. Renes, I. Van Seuningen, The human mucin MUC4 is transcriptionally regulated by caudal-related homeobox, hepatocyte nuclear factors, forkhead box A, and GATA endodermal transcription factors in epithelial cancer cells. J. Biol. Chem. 282, 22638–22650 (2007)PubMedCrossRef

13.

G.A. Kozloski, C.A. Carraway, K.L. Carraway, Mechanistic and signaling analysis of Muc4-ErbB2 signaling module: new insights into the mechanism of ligand-independent ErbB2 activity. J. Cell. Physiol. 224, 649–657 (2010)PubMedCrossRef

14.

S. Ropero, M. Esteller, The role of histone deacetylases (HDACs) in human cancer. Mol. Oncol. 1, 19–25 (2007)PubMedCrossRef

15.

M. Esteller, CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 21, 5427–5440 (2002)PubMedCrossRef

16.

S. Minucci, P.G. Pelicci, Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 6, 38–51 (2006)PubMedCrossRef

17.

H.Y. Lin, C.S. Chen, S.P. Lin, J.R. Weng, Targeting histone deacetylase in cancer therapy. Med. Res. Rev. 26, 397–413 (2006)PubMedCrossRef

18.

A.J. Wilson, D.S. Byun, N. Popova, L.B. Murray, K. L’Italien, Y. Sowa, D. Arango, A. Velcich, L.H. Augenlicht, J.M. Mariadason, Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J. Biol. Chem. 281, 13548–13558 (2006)PubMedCrossRef

19.

N. Gurvich, O.M. Tsygankova, J.L. Meinkoth, P.S. Klein, Histone deacetylase is a target of valproic acid-mediated cellular differentiation. Cancer Res. 64, 1079–1086 (2004)PubMedCrossRef

20.

J.M. Mariadason, A. Velcich, A.J. Wilson, L.H. Augenlicht, P.R. Gibson, Resistance to butyrate-induced cell differentiation and apoptosis during spontaneous Caco-2 cell differentiation. Gastroenterology 120, 889–899 (2001)PubMedCrossRef

21.

J.M. Mariadason, K.L. Rickard, D.H. Barkla, L.H. Augenlicht, P.R. Gibson, Divergent phenotypic patterns and commitment to apoptosis of Caco-2 cells during spontaneous and butyrate-induced differentiation. J. Cell. Physiol. 183, 347–354 (2000)PubMedCrossRef

22.

S. Shankar, R.K. Srivastava, Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis. Adv. Exp. Med. Biol. 615, 261–298 (2008)PubMedCrossRef

23.

P.A. Marks, V.M. Richon, R.A. Rifkind, Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J. Natl. Cancer Inst. 92, 1210–1216 (2000)PubMedCrossRef

24.

M. Barshishat, S. Polak-Charcon, B. Schwartz, Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells. Br. J. Cancer 82, 195–203 (2000)PubMedCrossRef

25.

H.L. Newmark, J.R. Lupton, C.W. Young, Butyrate as a differentiating agent: pharmacokinetics, analogues and current status. Cancer Lett. 78, 1–5 (1994)PubMedCrossRef

26.

T. Vanhaecke, P. Papeleu, G. Elaut, V. Rogiers, Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view. Curr. Med. Chem. 11, 1629–1643 (2004)PubMedCrossRef

27.

D. Massillon, I.J. Arinze, C. Xu, F. Bone, Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha. J. Biol. Chem. 278, 40694–40701 (2003)PubMedCrossRef

28.

B. Schwartz, R.S. Bresalier, Y.S. Kim, The role of mucin in colon-cancer metastasis. Int. J. Cancer 52, 60–65 (1992)PubMedCrossRef

29.

I. Lavi, D. Levinson, I. Peri, Y. Tekoah, Y. Hadar, B. Schwartz, Chemical characterization, antiproliferative and antiadhesive properties of polysaccharides extracted from Pleurotus pulmonarius mycelium and fruiting bodies. Appl. Microbiol. Biotechnol. 85, 1977–1990 (2010)PubMedCrossRef

30.

I. Lavi, D. Levinson, I. Peri, L. Nimri, Y. Hadar, B. Schwartz, Orally administered glucans from the edible mushroom Pleurotus pulmonarius reduce acute inflammation in dextran sulfate sodium-induced experimental colitis. Br. J. Nutr. 103, 393–402 (2010)PubMedCrossRef

31.

B. Schwartz, V.O. Melnikova, C. Tellez, A. Mourad-Zeidan, K. Blehm, Y.J. Zhao, M. McCarty, L. Adam, M. Bar-Eli, Loss of AP-2alpha results in deregulation of E-cadherin and MMP-9 and an increase in tumorigenicity of colon cancer cells in vivo. Oncogene 26, 4049–4058 (2007)PubMedCrossRef

32.

M. Barshishat, I. Levi, D. Benharroch, B. Schwartz, Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line. Br. J. Cancer 87, 1314–1320 (2002)PubMedCrossRef

33.

S. Pizzi, C. Azzoni, E. Tamburini, L. Bottarelli, N. Campanini, T. D’Adda, G. Fellegara, T.V. Luong, C. Pasquali, G. Rossi, G. Delle Fave, R. Camisa, C. Bordi, G. Rindi, Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of beta-catenin and chromosomal instability. Endocr. Relat. Cancer 15, 1013–1024 (2008)PubMedCrossRef

34.

S. Kim, J.K. Kang, Y.K. Kim, D.W. Seo, S.H. Ahn, J.C. Lee, C.H. Lee, J.S. You, E.J. Cho, H.W. Lee, J.W. Han, Histone deacetylase inhibitor apicidin induces cyclin E expression through Sp1 sites. Biochem. Biophys. Res. Commun. 342, 1168–1173 (2006)PubMedCrossRef

35.

P.A. Marks, W.S. Xu, Histone deacetylase inhibitors: potential in cancer therapy. J. Cell. Biochem. 107, 600–608 (2009)PubMedCrossRef

36.

P. Hatzis, I. Talianidis, Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol. Cell. Biol. 21, 7320–7330 (2001)PubMedCrossRef

37.

T. Tanaka, S. Jiang, H. Hotta, K. Takano, H. Iwanari, K. Sumi, K. Daigo, R. Ohashi, M. Sugai, C. Ikegame, H. Umezu, Y. Hirayama, Y. Midorikawa, Y. Hippo, A. Watanabe, Y. Uchiyama, G. Hasegawa, P. Reid, H. Aburatani, T. Hamakubo, J. Sakai, M. Naito, T. Kodama, Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J. Pathol. 208, 662–672 (2006)PubMedCrossRef

38.

M. Sugai, H. Umezu, T. Yamamoto, S. Jiang, H. Iwanari, T. Tanaka, T. Hamakubo, T. Kodama, M. Naito, Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors. Pathol. Int. 58, 681–686 (2008)PubMedCrossRef

39.

R.S. Bresalier, Y. Niv, J.C. Byrd, Q.Y. Duh, N.W. Toribara, R.W. Rockwell, R. Dahiya, Y.S. Kim, Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis. J. Clin. Invest. 87, 1037–1045 (1991)PubMedCrossRef

40.

S.F. Kuan, J.C. Byrd, C.B. Basbaum, Y.S. Kim, Characterization of quantitative mucin variants from a human colon cancer cell line. Cancer Res. 47, 5715–5724 (1987)PubMed

41.

N. Yamada, Y. Nishida, H. Tsutsumida, M. Goto, M. Higashi, M. Nomoto, S. Yonezawa, Promoter CpG methylation in cancer cells contributes to the regulation of MUC4. Br. J. Cancer 100, 344–351 (2009)PubMedCrossRef

42.

H. Albrecht, K.L. Carraway 3rd, MUC1 and MUC4: switching the emphasis from large to small. Cancer Biother. Radiopharm. 26, 261–271 (2011)PubMedCrossRef

43.

M.A. Hollingsworth, B.J. Swanson, Mucins in cancer: protection and control of the cell surface. Nat. Rev. Cancer 4, 45–60 (2004)PubMedCrossRef

44.

K. Hosono, H. Endo, H. Takahashi, M. Sugiyama, T. Uchiyama, K. Suzuki, Y. Nozaki, K. Yoneda, K. Fujita, M. Yoneda, M. Inamori, A. Tomatsu, T. Chihara, K. Shimpo, H. Nakagama, A. Nakajima, Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinase. Mol. Carcinog. 49, 662–671 (2010)PubMedCrossRef

45.

K. Furukawa, T. Sato, T. Katsuno, T. Nakagawa, Y. Noguchi, A. Tokumasa, K. Yokote, O. Yokosuka, Y. Saito, Smad3 contributes to positioning of proliferating cells in colonic crypts by inducing EphB receptor protein expression. Biochem. Biophys. Res. Commun. 405, 521–526 (2011)PubMedCrossRef

46.

F.J. Kubben, A. Peeters-Haesevoets, L.G. Engels, C.G. Baeten, B. Schutte, J.W. Arends, R.W. Stockbrugger, G.H. Blijham, Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation. Gut 35, 530–535 (1994)PubMedCrossRef

47.

T. Saandi, F. Baraille, L. Derbal-Wolfrom, A.L. Cattin, F. Benahmed, E. Martin, P. Cardot, B. Duclos, A. Ribeiro, J.N. Freund, I. Duluc, Regulation of the tumor suppressor homeogene Cdx2 by HNF4alpha in intestinal cancer. Oncogene (2012)

48.

M. Ahmad, A. Hamid, A. Hussain, R. Majeed, Y. Qurishi, J.A. Bhat, R.A. Najar, A.K. Qazi, M.A. Zargar, S.K. Singh, A.K. Saxena, Understanding histone deacetylases in the cancer development and treatment: an epigenetic perspective of cancer chemotherapy, DNA cell. Biol. (2012)

49.

L. Peng, E. Seto, Deacetylation of nonhistone proteins by HDACs and the implications in cancer. Handb. Exp. Pharmacol. 206, 39–56 (2011)PubMedCrossRef

50.

H.S. Lee, M.H. Park, S.J. Yang, H.Y. Jung, S.S. Byun, D.S. Lee, H.S. Yoo, Y.I. Yeom, S.B. Seo, Gene expression analysis in human gastric cancer cell line treated with trichostatin A and S-adenosyl-L-homocysteine using cDNA microarray. Biol. Pharm. Bull. 27, 1497–1503 (2004)PubMedCrossRef

51.

J.M. Mariadason, G.A. Corner, L.H. Augenlicht, Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Cancer Res. 60, 4561–4572 (2000)PubMed

52.

J. Serpa, F. Caiado, T. Carvalho, C. Torre, L.G. Goncalves, C. Casalou, P. Lamosa, M. Rodrigues, Z. Zhu, E.W. Lam, S. Dias, Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells. J. Biol. Chem. 285, 39211–39223 (2010)PubMedCrossRef

53.

H. Yoshioka, H. Kamitani, T. Watanabe, T.E. Eling, Nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) expression is increased by the histone deacetylase inhibitor trichostatin A. J. Biol. Chem. 283, 33129–33137 (2008)PubMedCrossRef

54.

S. Paterson, K.L. Sin, J.M. Tiang, R.F. Minchin, N.J. Butcher, Histone deacetylase inhibitors increase human arylamine N-acetyltransferase-1 expression in human tumor cells. Drug Metab. Dispos. 39, 77–82 (2011)PubMedCrossRef

55.

L. Pufahl, C. Katryniok, N. Schnur, B.L. Sorg, J. Metzner, M. Grez, D. Steinhilber, Trichostatin A induces 5-lipoxygenase promoter activity and mRNA expression via inhibition of histone deacetylase 2 and 3. J. Cell. Mol. Med. (2011)

56.

T. Suzuki, A. Kimura, R. Nagai, M. Horikoshi, Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Sp1 on and through DNA binding. Genes Cells 5, 29–41 (2000)PubMedCrossRef

57.

S. Zhao, K. Venkatasubbarao, S. Li, J.W. Freeman, Requirement of a specific Sp1 site for histone deacetylase-mediated repression of transforming growth factor beta Type II receptor expression in human pancreatic cancer cells. Cancer Res. 63, 2624–2630 (2003)PubMed

Titel: Epigenetic control of HNF-4α in colon carcinoma cells affects MUC4 expression and malignancy
verfasst von: Anna Algamas-Dimantov
Einav Yehuda-Shnaidman
Irena Peri
Betty Schwartz
Publikationsdatum: 01.04.2013
Verlag: Springer Netherlands
Erschienen in: Cellular Oncology / Ausgabe 2/2013
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-012-0123-3

Neu im Fachgebiet Pathologie

01.04.2024 | Forensische Traumatologie | CME

Springer Medizin

Epigenetic control of HNF-4α in colon carcinoma cells affects MUC4 expression and malignancy

Abstract

Background

Results

Conclusions

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien

Springer Medizin

Abstract

Background

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2013

Chromosome 1q25.3 copy number alterations in primary breast cancers detected by multiplex ligation-dependent probe amplification and allelic imbalance assays and its comparison with fluorescent in situ hybridization assays

Erratum to: Chlorophyllin abrogates canonical Wnt/β-catenin signaling and angiogenesis to inhibit the development of DMBA-induced hamster cheek pouch carcinomas

Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer

Restoration of klotho expression induces apoptosis and autophagy in hepatocellular carcinoma cells

SLUG silencing increases radiosensitivity of melanoma cells in vitro

CD81 is a candidate tumor suppressor gene in human gastric cancer

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien