title: Orofacial and gastrointestinal hyperplasia and neoplasia in smad4+/- and elf+/-/smad4+/- mutant mice.
abstract: BACKGROUND
  Smad4 is vital to the roles of Smads 2 and 3 in transforming growth factor-beta (TGF)-beta signal transduction, and inactivated Smad4 is common to human gastrointestinal cancers. The embryonic liver fodrin (ELF) is a beta-spectrin that facilitates the nuclear translocation of activated Smad4.
  
  
  METHODS
  Smad4+/- mice, known to develop gastrointestinal cancer, were crossbred with elf+/- mice. The smad4+/- and smad4+/-/elf+/- offspring were autopsied as abnormalities developed.
  
  
  RESULTS
  In addition to polyps and adenocarcinomas of the stomach and duodenum, the smad4+/- mice developed squamous cell carcinomas of the skin, oral mucosa and forestomach, benign neoplasms of connective tissue and lacrimal gland, and a lymphoma. The smad4+/-/elf+/- mice developed extensive hyperplasia and neoplasia of the gastric mucosa.
  
  
  CONCLUSIONS
  These findings indicate that investigating interactions among smad4, elf, and other genes involved in TGF-beta signaling should be useful in further delineating the processes of neoplasia in a wide variety of tissues.
authors.affiliation: Oral Pathology Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA. oralpath@erols.com
authors.forename: Robert S
authors.initials: RS
authors.lastname: Redman
authors.forename: Varalakshmi
authors.initials: V
authors.lastname: Katuri
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Allan
authors.initials: A
authors.lastname: Dillner
authors.forename: Bibhuti
authors.initials: B
authors.lastname: Mishra
authors.forename: Lopa
authors.initials: L
authors.lastname: Mishra
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics; D006824:Hybridization, Genetic; D006965:Hyperplasia / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009062:Mouth Neoplasms / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051901:Smad4 Protein; D015534:Trans-Activators