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1. Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett’s Esophagus: Regulation via Dickkopf-1

Author

Orestis Lyros, Parvaneh Rafiee, Linghui Nie, Rituparna Medda, Nebojsa Jovanovic, Mary F. Otterson, Behnaz Behmaram, Ιnes Gockel, Alexander Mackinnon, and Reza Shaker

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

INTRODUCTION: Wnt/β-catenin signaling activation has been reported only during the late steps of Barrett’s esophagus (BE) neoplastic progression, but not in BE metaplasia, based on the absence of nuclear β-catenin. However, β-catenin transcriptional activity has been recorded in absence of robust nuclear accumulation. Thus, we aimed to investigate the Wnt/β-catenin signaling in nondysplastic BE. METHODS: Esophageal tissues from healthy and BE patients without dysplasia were analyzed for Wnt target gene expression by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Esophageal squamous (EPC1-& EPC2-hTERT), BE metaplastic (CP-A), and adenocarcinoma (OE33) cell lines were characterized for Wnt activation by qRT-PCR, Western blot, and luciferase assay. Wnt activity regulation was examined by using recombinant Wnt3a and Dickkopf-1 (Dkk1) as well as Dkk1 short interfering RNA. RESULTS: Wnt target genes (AXIN2, c-MYC, Cyclin D1, Dkk1) and Wnt3a were significantly upregulated in nondysplastic BE compared with squamous mucosa. Elevated levels of dephosphorylated β-catenin were detected in nondysplastic BE. Nuclear active β-catenin and TOPflash activity were increased in CP-A and OE33 cells compared with squamous cells. Wnt3a-mediated β-catenin signaling activation was abolished by Dkk1 in CP-A cells. TOPFlash activity was elevated following Dkk1 silencing in CP-A but not in OE33 cells. Dysplastic and esophageal adenocarcinoma tissues demonstrated further Dkk1 and AXIN2 overexpression. CONCLUSIONS: Despite the absence of robust nuclear accumulation, β-catenin is transcriptionally active in nondysplastic BE. Dkk1 overexpression regulates β-catenin signaling in BE metaplastic but not in adenocarcinoma cells, suggesting that early perturbation of Dkk1-mediated signaling suppression may contribute to BE malignant transformation.

Published
2015
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2. Contributors

Author

Andrea M. Abbott, Herand Abcarian, Wasef Abu-Jaish, David B. Adams, Julie E. Adams, Andrew S. Akman, Steven R. Alberts, Hisami Ando, Leonard Armstrong, Vivian A. Asamoah, Theodor Asgeirsson, Stanley W. Ashley, Dimitrios Avgerinos, H. Randolph Bailey, Humayun Bakhtawar, Santhoshi Bandla, John M. Barlow, Todd H. Baron, Juan Camilo Barreto Andrade, Lokesh Bathla, Jennifer S. Beaty, David E. Beck, David Beddy, Alec C. Beekley, Kevin E. Behrns, Kfir Ben-David, Jacques Bergman, Marc Besselink, Adil E. Bharucha, Adrian Billeter, Sylvester M. Black, Jeffrey A. Blatnik, Ronald Bleday, Brendan J. Boland, Scott J. Boley, Luigi Bonavina, Eduardo A. Bonin, Sarah Y. Boostrom, Thomas C. Bower, Jan Brabender, Malcolm V. Brock, Jill C. Buckley, William J. Bulsiewicz, Adele Burgess, Sathyaprasad C. Burjonrappa, Angel M. Caban, Jason A. Call, Mark P. Callery, John L. Cameron, Michael Camilleri, Peter W.G. Carne, Jennifer C. Carr, Emily Carter Paulson, Riaz Cassim, Donald O. Castell, Peter Cataldo, Samuel Cemaj, Parakrama T. Chandrasoma, George J. Chang, Vivek Chaudhry, Herbert Chen, Clifford S. Cho, Eugene A. Choi, Karen Chojnacki, Michael A. Choti, John D. Christein, Donald O. Christensen, Chike V. Chukwumah, Albert K. Chun, Robert R. Cima, Clancy J. Clark, Pierre-Alain Clavien, Alfred M. Cohen, Jeffrey Cohen, Steven D. Colquhoun, Willy Coosemans, Gene F. Coppa, Edward E. Cornwell, Daniel A. Cortez, Mario Costantini, Daniel A. Craig, Peter F. Crookes, Joseph J. Cullen, Alexandre d’Audiffret, Herbert Decaluwé, Georges Decker, Thomas C.B. Dehn, Paul De Leyn, Steven R. DeMeester, Tom R. DeMeester, Aram N. Demirjian, Anthony L. DeRoss, Eduardo de Santibañes, John H. Donohue, Eric J. Dozois, Brian J. Dunkin, Stephen P. Dunn, Christy M. Dunst, Andre Duranceau, Noreen Durrani, Philipp Dutkowski, Barish H. Edil, Jonathan E. Efron, Yousef El-Gohary, E. Christopher Ellison, Scott A. Engum, Warren E. Enker, David A. Etzioni, Douglas B. Evans, Victor W. Fazio, Edward L. Felix, Aaron S. Fink, James Fisher, Robert J. Fitzgibbons, Evan L. Fogel, Yuman Fong, Debra H. Ford, Patrick Forgione, John B. Fortune, Danielle M. Fritze, Karl-Hermann Fuchs, Brian Funaki, Thomas R. Gadacz, Susan Galandiuk, David Geller, George K. Gittes, Christopher A. Gitzelmann, Tony E. Godfrey, Matthew I. Goldblatt, Hein G. Gooszen, Gregory J. Gores, Yogesh Govil, Kimberly Grant, Sarah E. Greer, Jay L. Grosfeld, José G. Guillem, Jeffrey A. Hagen, Jason F. Hall, Christopher L. Hallemeier, Peter T. Hallowell, Amy P. Harper, Ioannis S. Hatzaras, Elliott R. Haut, William S. Havron, Richard F. Heitmiller, J. Michael Henderson, H. Franklin Herlong, O. Joe Hines, Fuyuki Hirashima, Wayne L. Hofstetter, Arnulf H. Hölscher, Roel Hompes, Toshitaka Hoppo, Philip J. Huber, Tracy Hull, Eric S. Hungness, John G. Hunter, James E. Huprich, Hero K. Hussain, Neil Hyman, Jennifer L. Irani, Emily T. Jackson, Danny O. Jacobs, Eric H. Jensen, Catherine Jephcott, Blair A. Jobe, Michael Johnston, Jeffrey Jorden, Paul Joyner, Lucas A. Julien, Peter J. Kahrilas, Ronald Kaleya, Elika Kashef, Philip Katz, Tara Kent, Nadia J. Khati, Jonathan C. King, Nicole A. Kissane, Andrew S. Klein, Dean E. Klinger, Jennifer Knight, Issam Koleilat, Robert Kozol, Seth B. Krantz, Daniela Ladner, Alexander Langerman, David W. Larson, Simon Law, Leo P. Lawler, Konstantinos N. Lazaridis, Yi-Horng Lee, Yoori Lee, Jérémie H. Lefèvre, Glen A. Lehman, Toni Lerut, David M. Levi, Anne Lidor, Dorothea Liebermann-Meffert, Joseph Lillegard, Keith D. Lillemoe, Virginia R. Litle, Donald C. Liu, Edward V. Loftus, Miguel Lopez-Viego, Reginald V.N. Lord, Val J. Lowe, Georg Lurje, Calvin Lyons, Robert L. MacCarty, Robert D. Madoff, Anurag Maheshwari, Najjia N. Mahmoud, David M. Mahvi, Massimo Malagó, Patrick Mannal, Michael R. Marohn, David J. Maron, Joseph E. Martz, Kellie L. Mathis, Douglas Mathisen, Jeffrey B. Matthews, Laurence E. McCahill, David A. McClusky, David W. McFadden, Lee McHenry, Paul J. McMurrick, Anthony S. Mee, John E. Meilahn, Fabrizio Michelassi, Robert C. Miller, Thomas A. Miller, J. Michael Millis, Ryosuke Misawa, Sumeet Mittal, Ernesto P. Molmenti, John R.T. Monson, Jesse Moore, Katherine A. Morgan, Christopher R. Morse, Neil J. Mortensen, Melinda M. Mortenson, Ruth Moxon, Michael W. Mulholland, Ido Nachmany, Philippe Nafteux, David M. Nagorney, Govind Nandakumar, Bala Natarajan, Heidi Nelson, Jeffrey M. Nicastro, Ankesh Nigam, Nicholas N. Nissen, Jeffrey A. Norton, Michael Nussbaum, Scott Nyberg, Stefan Öberg, Daniel S. Oh, Jill K. Onesti, Robert W. O’Rourke, Aytekin Oto, Mary F. Otterson, James R. Ouellette, Charles N. Paidas, John E. Pandolfino, Harry T. Papaconstantinou, Theodore N. Pappas, Yann Parc, Susan C. Parker, Marco G. Patti, Walter Pegoli, John H. Pemberton, Jeffrey H. Peters, Thai H. Pham, Lakshmikumar Pillai, Carlos E. Pineda, Henry A. Pitt, Jeffrey L. Ponsky, Mitchell C. Posner, Russel G. Postier, Sangeetha Prabhakaran, Vivek N. Prachand, Florencia G. Que, Arnold Radtke, Rudra Rai, Jan Rakinic, David W. Rattner, Daniel P. Raymond, Thomas W. Rice, J. David Richardson, Martin Riegler, John Paul Roberts, Patricia L. Roberts, David A. Rodeberg, Kevin K. Roggin, Rolando Rolandelli, Sabine Roman, Ernest L. Rosato, Michael J. Rosen, Andrew Ross, Amy P. Rushing, Adheesh Sabnis, Theodore J. Saclarides, Peter M. Sagar, George H. Sakorafas, Leonard B. Saltz, Shawn N. Sarin, Michael G. Sarr, Kennith Sartorelli, Jeannie F. Savas, Bruce Schirmer, Christine Schmid-Tannwald, John G. Schneider, Paul M. Schneider, Thomas Schnelldorfer, David J. Schoetz, Sebastian Schoppmann, Wolfgang Schröder, Richard D. Schulick, Anthony Senagore, Boris Sepesi, Nicholas J. Shaheen, Stuart Sherman, Irene Silberstein, Clifford L. Simmang, George Singer, Douglas P. Slakey, Jason Smith, Jessica K. Smith, Christopher W. Snyder, Christopher J. Sonnenday, Nathaniel J. Soper, George C. Sotiropoulos, Stuart Jon Spechler, Andrew Stanley, Mindy B. Statter, Kimberley E. Steele, Emily Steinhagen, Luca Stocchi, Gary Sudakoff, Abhishek Sundaram, Magesh Sundaram, Lee L. Swanström, Daniel E. Swartz, Tadahiro Takada, Eric P. Tamm, Ali Tavakkolizadeh, Gordon L. Telford, Julie K. Marosky Thacker, Dimitra G. Theodoropoulos, Michael S. Thomas, Alan G. Thorson, Kristy Thurston, David S. Tichansky, Yutaka Tomizawa, L. William Traverso, Thadeus Trus, Susan Tsai, Vassiliki Liana Tsikitis, Steven Tsoraides, Radu Tutuian, Andreas G. Tzakis, Daniel Vallböhmer, Dirk Van Raemdonck, Hjalmar van Santvoort, Anthony C. Venbrux, Selwyn M. Vickers, Hugo V. Villar, Leonardo Villegas, James R. Wallace, William D. Wallace, Huamin Wang, Kenneth K. Wang, James L. Watkins, Thomas J. Watson, Irving Waxman, Martin R. Weiser, John Welch, Mark L. Welton, Steven D. Wexner, Rebekah R. White, Elizabeth C. Wick, Alison Wilson, Emily Winslow, Piotr Witkowski, Bruce G. Wolff, Christopher L. Wolfgang, W. Douglas Wong, Jonathan Worsey, Cameron D. Wright, Bhupender Yadav, Charles J. Yeo, Trevor M. Yeung, Max Yezhelyev, Kyo-Sang Yoo, Yi-Qian Nancy You, Tonia M. Young-Fadok, Johannes Zacherl, Giovanni Zaninotto, Merissa N. Zeman, Pamela Zimmerman, and Gregory Zuccaro

Published
2013
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3. Gastrointestinal Motility

Author

Michael G. Sarr, Mary F. Otterson, and Joseph J. Cullen

Subjects
medicine.medical_specialty, Gastric emptying, Stomach, digestive, oral, and skin physiology, Motility, chemistry.chemical_element, Smooth muscle contraction, Biology, Calcium, Gastroenterology, Calcium in biology, Cell biology, medicine.anatomical_structure, chemistry, Internal medicine, medicine, Large intestine, Intracellular
Abstract

This chapter discusses the physiology of smooth muscle contraction of the gut, with special reference to aspects of the techniques to measure contractile activity. Gastrointestinal (GI) motility depends on the presence of contractile activity within the gut to create the forces that move intestinal content distally (or proximally during vomiting). One might choose to measure contractile activity either directly or indirectly, or to measure the movement/transit of the luminal content out of the stomach (gastric emptying), through the small and/or large intestine (intestinal transit), and finally its discharge from the gut (defecation). GI motility ultimately depends on intestinal smooth muscle contractions that generate the force needed to move intraluminal content along the gut. The final common pathway of intestinal smooth muscle contractions depends on the intracellular release of calcium. Once liberated, the intracellular calcium induces the intracellular mechanisms controlling interaction of contractile proteins leading to cell shortening.

Published
2001
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4. Contributors

Author

William M. Abbott, Steve F. Abcouwer, N. Scott Adzick, Samuel S. Ahn, David C. Allison, J.B. Ames, Keith D. Amos, Robert W. Anderson, Jeffrey M. Arbeit, Sonia Y. Archer, Arlene S. Ash, Stanley W. Ashley, Anthony Atala, Alfred Ayala, Matthew D. Bacchetta, Charles M. Balch, Anirban Banerjee, Adrian Barbul, Philip S. Barie, Clyde F. Barker, Jeffrey S. Barkun, Robert E. Barrow, Harry D. Bear, Russell S. Berman, Walter L. Biffl, Timothy R. Billiar, John D. Birkmeyer, Timothy G. Buchman, Eileen M. Bulger, Charles B. Cairns, Casey Calkins, William G. Cance, Irshad H. Chaudry, Cynthia S. Chin, Gyu S. Chin, Alexander W. Clowes, Lisa Colletti, Joy L. Collins, Suzy Conway, Clay Cothren, Christopher A. Crisera, Joseph J. Cullen, P. William Curreri, James C. Cusack, Roger E. De Filippo, Edwin A. Deitch, E. Patchen Dellinger, Achilles A. Demetriou, Jeffrey A. Drebin, Soumitra R. Eachempati, Timothy J. Eberlein, David T. Efron, Nancy R. Ehrlich, Theresa L. Eisenbraun, Lee M. Ellis, Darwin Eton, B. Mark Evers, Liane Feldman, Mitchell P. Fink, Joseph J. Fins, David R. Fischer, Josef E. Fischer, Alan W. Flake, Raquel M. Forsythe, Bradley D. Freeman, Fabia Gamboni-Robertson, R. Neal Garrison, James Garvey, M. Gasser, Jonathan Gertler, Anna Getselman, George K. Gittes, Matthew I. Goldblatt, Paul J. Gorman, Douglas W. Green, David G. Greenhalgh, Jurgen Hannig, Alden H. Harken, Per-Olof Hasselgren, Julie Heimbach, Peter K. Henke, David N. Herndon, Graham L. Hill, Richard A. Hodin, Susan D. Horn, Lisa I. Iezzoni, Daniel Inderbitzen, Svetlana Ivanova, Danny O. Jacobs, Daniel B. Jones, Mary Jane Kagarise, Gordon L. Kauffman, Richard D. Kenagy, Gregory D. Kennedy, Jerald J. Killion, Denise E. Kirschner, Thomas M. Krummel, Alexander Sasha Krupnick, I.L. Laskowski, Robert D. Lasley, Stephen R. Lauterbach, Jeffrey H. Lawson, Raphael C. Lee, David Lee-Parritz, David C. Linehan, Jean Y. Liu, Michael T. Longaker, Charles Lucey, Nancy R. Macdonald, Ronald V. Maier, Thomas S. Maldonado, John C. Marshall, Takeaki Matsuda, Jeffrey B. Matthews, David T. Mauger, Lucretia W. McClure, Jonathan L. Meakins, Andreas H. Meier, Robert M. Mentzer, Tanya K. Meyer, Rebecca M. Minter, Lyle L. Moldawer, Ernest E. Moore, Daniel Most, Caren M. Mulford, Michael W. Mulholland, Joseph Murphy, Rene J.P. Musters, Thomas A. Mustoe, Daniel D. Myers, Attila Nakeeb, Avery B. Nathens, Andrea L. Nestor, John E. Niederhuber, Keith O'Rourke, Marshall J. Orloff, Mary F. Otterson, Wayne R. Patterson, Timothy M. Pawlik, Henry A. Pitt, Lindsay D. Plank, Timothy A. Pritts, R. Lawrence Reed, Robert V. Rege, Robert S. Rhodes, Henry E. Rice, Martin Riegler, Kyung M. Ro, Thomas N. Robinson, John L. Rombeau, Joseph M. Rosen, Ori D. Rotstein, Jacek Rozga, Justin T. Sambol, Michael G. Sarr, Alexandrina Saulis, Mary C. Schuerman, Martin G. Schwacha, Patrica M. Scott, Patricia A. Sheiner, George F. Sheldon, Michael Shwartz, H. Hank Simms, Marcus K. Simpson, Clay Smith, Scott D. Somers, Wiley W. Souba, David A. Spain, Jason A. Spector, Michael L. Steer, Bruce R. Stevens, Robert W. Storms, Kenneth K. Tanabe, James C. Thompson, N.L. Tilney, Daniel L. Traber, Kevin J. Tracey, Richard H. Turnage, A. Simon Turner, Thomas C. Vary, Gus J. Vlahakes, Yoram Vodovotz, Thomas W. Wakefield, Ping Wang, Glenn D. Warden, Brad W. Warner, Stephen M. Warren, James M. Watters, Ronald J. Weigel, Frank J. Wessels, Edward E. Whang, D. Whitley, James Willey, Douglas W. Wilmore, Robert R. Wolfe, Shirley K. Wrobleski, George P. Yang, Heidi Yeh, Barbara A. Zehnbauer, and Moritz M. Ziegler

Published
2001
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