Betacellulin stimulates growth of the mouse intestinal epithelium and increases adenoma multiplicity in Apc+/Min mice.
We employed transgenic mice overexpressing betacellulin (BTC) to study its effects in the gut. BTC stimulated crypt cell proliferation and markedly increased intestinal size, while the crypt-villus architecture was preserved. Introduction of a dominant negative epidermal growth factor receptor (EGFR) completely abolished the intestinal hyperplasia. BTC increased polyp multiplicity but did not change the mean size or the histological quality of intestinal polyps in Apc(+/Min) mice. Analysis of intact and cleaved caspase-3 levels indicated that BTC has anti-apoptotic effects in the intestinal epithelium. We conclude that increased BTC levels support the survival of nascent adenomas in Apc(+/Min) mice, resulting in a larger total polyp number at later stages.
Dahlhoff
Maik
M
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Feodor-Lynen-Strasse 25, Munich, Germany.
Horst
David
D
Gerhard
Markus
M
Kolligs
Frank T
FT
Wolf
Eckhard
E
Schneider
Marlon R
MR
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D066259:Betacellulin; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology*; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics
D025601:Adenomatous Polyposis Coli Protein; D066259:Betacellulin; C587852:Btc protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D066246:ErbB Receptors