abi3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescenceabi3异位表达降低体外和体内细胞生长特性而诱导衰老.pdfVIP

Latini et al. BMC Cancer 2011, 11:11 /1471-2407/11/11 RESEARCH ARTICLE Open Access ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence 1 1 1 1 2 1* Flavia RM Latini , Jefferson P Hemerly , Beatriz CG Freitas , Gisele Oler , Gregory J Riggins , Janete M Cerutti 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 charac