Abstract
Hyperactivation of the epidermal growth factor receptor (EGFR) in gastric cells due to excess of its ligand transforming growth factor-α (TGFA) is associated with hyperplastic lesions in Ménétrier's disease patients and in transgenic mice. Other EGFR ligands, however, have never been associated with stomach diseases. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) results in a severe, age-dependent hyperplasia of foveolar epithelium. The stomach weight of affected mice reached up to 3g representing more than 10% of total body weight. The preexisting corpus mucosa was severely depleted, and both parietal and chief cells were replaced by proliferating foveolar epithelium. The lesions were more severe in male as compared to female transgenic mice, and partially regressed in the former after castration-mediated androgen removal. The gastric hyperplasia fully disappeared when BTC-tg mice were crossed into the Egfr(Wa5) background expressing a dominant-negative EGFR, indicating that the phenotype is EGFR-dependent. This is, to our knowledge, the first report of hyperplastic gastric lesions due to the overexpression of an EGFR ligand other than TGFA. BTC-tg mice are therefore a new, promising model for studyi...Continue Reading
References
Sep 1, 1977·Postgraduate Medical Journal·O Hernández-Pieretti
May 11, 1975·Annals of Surgery·H W ScottD L Page
Sep 1, 1992·The Journal of Clinical Investigation·H TakagiG Merlino
Dec 1, 1988·Annals of Surgery·T M SundtR A Malt
Nov 1, 1987·Gut·B LarsenE Kristensen
Feb 1, 1995·Gastroenterology·D E BockmanG Merlino
Apr 1, 1996·Digestive Diseases and Sciences·J R GoldenringR J Coffey
Jan 1, 1997·The Journal of Clinical Investigation·C C TsaiJ J Billadello
Apr 18, 1998·Oncogene·R Pinkas-KramarskiY Yarden
Feb 10, 2000·Annals of the New York Academy of Sciences·P NørgaardH L Moses
Dec 7, 2000·The New England Journal of Medicine·J S BurdickR J Coffey
May 16, 2001·Annals of Surgical Oncology·D A WirtzfeldM A Rodriguez-Bigas
Mar 22, 2003·Experimental Cell Research·Raymond C HarrisRobert J Coffey
Apr 28, 2004·Cytokine & Growth Factor Reviews·Richard Wing Chuen Wong, Laurent Guillaud
Sep 16, 2004·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Daekee LeeDavid W Threadgill
Sep 24, 2005·Endocrinology·Marlon R SchneiderEckhard Wolf
Jan 4, 2007·The Journal of Clinical Investigation·Robert J CoffeyMichael C Heinrich
Jul 20, 2007·Arquivos De Gastroenterologia·Drausio Jefferson MoraisNelson Adami Andreollo
Nov 14, 2008·Journal of Cellular Physiology·Marlon R Schneider, Eckhard Wolf
Nov 28, 2008·Digestive Diseases and Sciences·Richa Jain, Runjan Chetty
Dec 18, 2008·PloS One·Sara K LindénMichael A McGuckin
Citations
Jan 21, 2014·Seminars in Cell & Developmental Biology·Maik DahlhoffMarlon R Schneider
May 7, 2015·Experimental and Molecular Pathology·Helene SchulzThomas Klonisch
Jan 27, 2016·Journal of Gastroenterology and Hepatology·Ashleigh R PohTracy L Putoczki
Jul 1, 2016·Physiological Reviews·Jianchun ChenRaymond C Harris
Jul 17, 2019·JFMS Open Reports·Emi N BarkerNicolette J Hayward