ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence

Author(s)

Latini, Flavia R. M. ^{[1, 2]} ; Hemerly, Jefferson P. ^{[1, 2]} ; Freitas, Beatriz C. G. ^{[1, 2]} ; Oler, Gisele ^{[1, 2]} ; Riggins, Gregory J. ^[3] ; Cerutti, Janete M. ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Div Endocrinol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Genet Bases Thyroid Tumors Lab, Div Genet, Sao Paulo - Brazil

^[3] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 - USA

• Document type: Journal article
• Source: BMC CANCER; v. 11, JAN 11 2011.
• Web of Science Citations: 14

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. (AU)

• FAPESP's process: 05/60330-8 - Molecular markers in diagnosis and prognosis of patients with tumors of the human thyroid: transition from basic to clinical research
• Grantee: Janete Maria Cerutti
• Support Opportunities: Research Projects - Thematic Grants