title: ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence.
abstract: BACKGROUND
  Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.
  
  
  METHODS
  The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP). We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent.
  
  
  RESULTS
  We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression.
  
  
  CONCLUSIONS
  Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.
authors.affiliation: Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics and Division of Endocrinology, Universidade Federal de São Paulo, SP, Brazil.
authors.forename: Flavia R M
authors.initials: FR
authors.lastname: Latini
authors.forename: Jefferson P
authors.initials: JP
authors.lastname: Hemerly
authors.forename: Beatriz C G
authors.initials: BC
authors.lastname: Freitas
authors.forename: Gisele
authors.initials: G
authors.lastname: Oler
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C541989:ABI3 protein, human; C439569:ABI3BP protein, human; D048868:Adaptor Proteins, Signal Transducing; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases