LATS Young Investigator Awards

Flavia Roche Moreira Latini

Winner 2007

RE-expression of ABI3BP and ABI3 in human thyroid carcinoma cell LINES promotes senescence and INHIBITS CELL growth, migration, invasion and tumor growth F. R. M. Latini1,3, J. P. Hemerly2, G. J. Riggins4, and J. M. Cerutti1,3

1 Division of Genetics, Department of Morphology, 2 Division of Biophysics, Department of Biophysics and 3 Laboratory of Genetic Bases of Thyroid Tumors, Federal University of São Paulo, Brazil; and 4 Department of Neurosurgery, Johns Hopkins University Medical School, Baltimore, Maryland, USA.

Using Serial Analysis of Gene Expression we identified a transcript that was present in Follicular Thyroid Adenoma (FTA) and normal thyroid libraries while it was under-expressed in the Follicular Thyroid Carcinoma (FTC) library, suggesting that the lost of its expression could be associated to FTC’s pathogenesis. The transcript encodes a protein named ABI3BP. Although ABI3BP was first described as a target of ABI3, a protein involved in cell migration and metastases, its biological function still remains unknown. To investigate whether the loss of expression of ABI3BP and ABI3 could be associated with thyroid tumor progression, we first cloned the full length cDNA of ABI3BP and ABI3 into pcDNA vector. The constructs were stably transfected into two human thyroid carcinoma cell lines that do not expresses these transcripts. Subsequently, we evaluated the effect of ABI3BP and ABI3 re-expression on cell growth, apoptosis, senescence, cell motility, invasion, and tumor growth. At least two clones from each transfectant were tested. Clones expressing ABI3BP showed reduced proliferation, migration, inhibited Matrigel invasion and promoted cellular senescence. These in vitro observations are in agreement with in vivo analysis, given that cells re-expressing ABI3BP extinguished or reduced tumor growth in nude mice. Likewise, ABI3 expressing clones decreased migration, invasion and tumor formation in nude mice. These findings represent the first experimental evidence showing that the loss of expression of ABI3BP and ABI3 may modulate thyroid tumor progression. Supported by Fapesp and CNPq.