Cell Growth & Differentiation, Vol 7, Issue 5 647-653, Copyright © 1996 by American Association of Cancer Research

ARTICLES

Cellular growth state differentially regulates enterocyte gene expression in butyrate-treated HT-29 cells

RA Hodin, S Meng, S Archer and R Tang
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.

Enterocyte differentiation occurs at the crypt-villus junction through the transcriptional activation of cell-specific genes, including the brush-border enzyme intestinal alkaline phosphatase (IAP) and the microvillar structural protein, villin. Based upon previous in vivo studies demonstrating that IAP and villin are differentially affected by alterations in epithelial growth state, we examined the regulation of these two genes in an in vitro model of enterocyte differentiation. HT-29 cells were maintained in DMEM + 10% FCS and treated with sodium butyrate to induce enterocyte differentiation. Cell count and [3H]thymidine measurements confirm that sodium butyrate causes a marked decrease in cellular growth state, consistent with the differentiation process. Northern blot analyses revealed time- and dose-dependent increases (P < 0.001) in steady-state IAP and villin mRNA levels. The increases in both IAP and villin expression were dependent upon the presence of one or more newly synthesized proteins. Post-confluence and serum starvation were used to cause cell cycle withdrawal prior to the differentiation process. As predicted from our previous in vivo data, villin expression was unaffected by changes in cellular growth state, whereas IAP expression was dramatically diminished under hypoproliferative conditions. We conclude that early withdrawal from the cell cycle alters the course of enterocyte differentiation, specifically decreasing IAP expression.

This article has been cited by other articles:

				R. F. Goldberg, W. G. Austen Jr., X. Zhang, G. Munene, G. Mostafa, S. Biswas, M. McCormack, K. R. Eberlin, J. T. Nguyen, H. S. Tatlidede, et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition PNAS, March 4, 2008; 105(9): 3551 - 3556. [Abstract] [Full Text] [PDF]

				M. S. Malo, M. Mozumder, X. B. Zhang, S. Biswas, A. Chen, L.-C. Bai, J. L. Merchant, and R. A. Hodin Intestinal alkaline phosphatase gene expression is activated by ZBP-89 Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G737 - G746. [Abstract] [Full Text] [PDF]

				S. Y. Archer, J. Johnson, H.-J. Kim, Q. Ma, H. Mou, V. Daesety, S. Meng, and R. A. Hodin The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G696 - G703. [Abstract] [Full Text] [PDF]

				C. Bazzini, V. Vezzoli, C. Sironi, S. Dossena, A. Ravasio, S. De Biasi, M. Garavaglia, S. Rodighiero, G. Meyer, U. Fascio, et al. Thiazide-sensitive NaCl-cotransporter in the Intestine: POSSIBLE ROLE OF HYDROCHLOROTHIAZIDE IN THE INTESTINAL Ca2+ UPTAKE J. Biol. Chem., May 20, 2005; 280(20): 19902 - 19910. [Abstract] [Full Text] [PDF]

				X. Tong, L. Yin, S. Joshi, D. W. Rosenberg, and C. Giardina Cyclooxygenase-2 Regulation in Colon Cancer Cells: MODULATION OF RNA POLYMERASE II ELONGATION BY HISTONE DEACETYLASE INHIBITORS J. Biol. Chem., April 22, 2005; 280(16): 15503 - 15509. [Abstract] [Full Text] [PDF]

				B. F. Hinnebusch, A. Siddique, J. W. Henderson, M. S. Malo, W. Zhang, C. P. Athaide, M. A. Abedrapo, X. Chen, V. W. Yang, and R. A. Hodin Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G23 - G30. [Abstract] [Full Text] [PDF]

				J. Zhang, H. Wong, S. Ramanan, D. Cheong, A. Leong, and S. C. Hooi The Proline-Rich Acidic Protein Is Epigenetically Regulated and Inhibits Growth of Cancer Cell Lines Cancer Res., October 15, 2003; 63(20): 6658 - 6665. [Abstract] [Full Text] [PDF]

				T. Kurita-Ochiai, S. Amano, K. Fukushima, and K. Ochiai Cellular Events Involved in Butyric Acid-Induced T Cell Apoptosis J. Immunol., October 1, 2003; 171(7): 3576 - 3584. [Abstract] [Full Text] [PDF]

				T. Kurita-Ochiai, K. Ochiai, N. Suzuki, K. Otsuka, and K. Fukushima Human Gingival Fibroblasts Rescue Butyric Acid-Induced T-Cell Apoptosis Infect. Immun., May 1, 2002; 70(5): 2361 - 2367. [Abstract] [Full Text] [PDF]

				B. F. Hinnebusch, S. Meng, J. T. Wu, S. Y. Archer, and R. A. Hodin The Effects of Short-Chain Fatty Acids on Human Colon Cancer Cell Phenotype Are Associated with Histone Hyperacetylation J. Nutr., May 1, 2002; 132(5): 1012 - 1017. [Abstract] [Full Text] [PDF]

				R. R. Rosato, J. A. Almenara, L. Cartee, V. Betts, S. P. Chellappan, and S. Grant The Cyclin-dependent Kinase Inhibitor Flavopiridol Disrupts Sodium Butyrate-induced p21WAF1/CIP1 Expression and Maturation while Reciprocally Potentiating Apoptosis in Human Leukemia Cells Mol. Cancer Ther., February 1, 2002; 1(4): 253 - 266. [Abstract] [Full Text] [PDF]

				T. Kurita-Ochiai, K. Ochiai, and K. Fukushima Butyric Acid-Induced T-Cell Apoptosis Is Mediated by Caspase-8 and -9 Activation in a Fas-Independent Manner Clin. Vaccine Immunol., March 1, 2001; 8(2): 325 - 332. [Abstract] [Full Text] [PDF]

				J. T. Wu, S. Y. Archer, B. Hinnebusch, S. Meng, and R. A. Hodin Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis Am J Physiol Gastrointest Liver Physiol, March 1, 2001; 280(3): G482 - G490. [Abstract] [Full Text] [PDF]

				C. Hadjiagapiou, L. Schmidt, P. K. Dudeja, T. J. Layden, and K. Ramaswamy Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1 Am J Physiol Gastrointest Liver Physiol, October 1, 2000; 279(4): G775 - G780. [Abstract] [Full Text] [PDF]

				S Siavoshian, J-P Segain, M Kornprobst, C Bonnet, C Cherbut, J-P Galmiche, and H M Blottiere Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression Gut, April 1, 2000; 46(4): 507 - 514. [Abstract] [Full Text] [PDF]

				L. E. Harrison, Q. M. Wang, and G. P. Studzinski Butyrate-Induced G2/M Block in Caco-2 Colon Cancer Cells is Associated with Decreased p34cdc2 Activity Experimental Biology and Medicine, November 1, 1999; 222(2): 150 - 156. [Abstract] [Full Text]

				J. H. Kim, S. Meng, A. Shei, and R. A. Hodin A novel Sp1-related cis element involved in intestinal alkaline phosphatase gene transcription Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G800 - G807. [Abstract] [Full Text] [PDF]

				K. Ishiguro and A. C. Sartorelli Coinduction of Embryonic and Adult-Type Globin mRNAs by Sodium Butyrate and Trichostatin A in Two Murine Interleukin-3-Dependent Bone Marrow-Derived Cell Lines Blood, December 1, 1998; 92(11): 4383 - 4393. [Abstract] [Full Text] [PDF]

				X. Gao, T. Sedgwick, Y.-B. Shi, and T. Evans Distinct Functions Are Implicated for the GATA-4, -5, and -6 Transcription Factors in the Regulation of Intestine Epithelial Cell Differentiation Mol. Cell. Biol., May 1, 1998; 18(5): 2901 - 2911. [Abstract] [Full Text]

				K. Nakano, T. Mizuno, Y. Sowa, T. Orita, T. Yoshino, Y. Okuyama, T. Fujita, N. Ohtani-Fujita, Y. Matsukawa, T. Tokino, et al. Butyrate Activates the WAF1/Cip1 Gene Promoter through Sp1 Sites in a p53-negative Human Colon Cancer Cell Line J. Biol. Chem., August 29, 1997; 272(35): 22199 - 22206. [Abstract] [Full Text] [PDF]