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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0079v1 15/3/787    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Latini, F. Articles by Cerutti, J. Search for Related Content PubMed PubMed Citation Articles by Latini, F. Articles by Cerutti, J.

F Latini, Morphology and Genetics, Federal University of Sao Paulo, Sao Paulo , Brazil
J Hemerly, Biophysics, Federal University of São Paulo, São Paulo , Brazil
G Oler, Morphology, Federal University of São Paulo, São Paulo , Brazil
G Riggins, Neurosurgery, Johns Hopkins Medical School, Baltimore, United States
J Cerutti, Morphology and Genetics, Federal University of Sao Paulo, Sao Paulo , Brazil

Correspondence: Flavia Latini, Email: flavia.latini{at}unifesp.br

Abstract

Loss of ABI gene family member 3 binding protein (ABI3BP) expression may be functionally involved in the pathogenesis of cancer. Previous reports have indicated a loss of expression in lung cancer and a presumed role in inducing cellular senescence. We show here that ABI3BP expression is significantly decreased in most malignant thyroid tumors of all types. To better understand ABI3BP’s role we created a model by re-expressing ABI3BP in two thyroid cancer cell lines. Re-expression of ABI3BP in thyroid cells resulted in a decrease in transforming activity, cell growth, cell viability, migration, invasion and tumor growth in nude mice. ABI3BP re-expression appears to trigger cellular senescence through the p21 pathway. Additionally, ABI3BP induced formation of HP1-positive senescence-associated heterochromatin foci (SAHF) and accumulation of senescence-associated β-galactosidase. The combination of a decrease in cell growth, invasion and other effects upon ABI3BP re-expression in vitro helps explain the large reduction in tumor growth we observed in nude mice. Together, our data provides evidence that the loss of ABI3BP expression could play a functional role in thyroid tumorigenesis. Activation of ABI3BP or its pathway may represent a possible basis for targeted therapy of certain cancers.