Stathmin is dispensable for tumor onset in mice.

Abstract

The microtubule-destabilizing protein stathmin is highly expressed in several types of tumor, thus deserving the name of oncoprotein 18. High levels of stathmin expression and/or activity favor the metastatic spreading and mark the most aggressive tumors, thus representing a realistic marker of poor prognosis. Stathmin is a downstream target of many signaling pathways, including Ras-MAPK, PI3K and p53, involved in both tumor onset and progression. We thus hypothesized that stathmin could also play a role during the early stages of tumorigenesis, an issue completely unexplored. In order to establish whether stathmin expression is necessary for tumor initiation, we challenged wild type (WT), stathmin heterozygous and stathmin knock-out (KO) mice with different carcinogens. Using well-defined mouse models of carcinogenesis of skin, bladder and muscle by the means of 7,12-dimethylbenz[α]antracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) and 3-methylcholanthrylene (3MC) treatments, respectively, we demonstrated that knock-out of stathmin has no impact on the onset of cancer in mice. No significant difference was noticed either when the Ras oncogene was mutated (skin carcinogenesis model) or when the p53 pathway was inactivated (bladder carcinomas and fibrosarcomas). Finally, we concomitantly impinged on p53 and Ras pathways, by generating WT and stathmin KO mouse embryo fibroblasts transformed with papilloma virus large T antigen (LgTAg) plus the K-Ras(G12V) oncogene. In vivo growth of xenografts from these transformed fibroblasts did not highlight any significant difference depending on the presence or absence of stathmin. Overall, our work demonstrates that stathmin expression is dispensable for tumor onset, at least in mice, thus making stathmin a virtually exclusive marker of aggressive disease and a promising therapeutic target for advanced cancers.

• Authors: Sara D'Andrea, Stefania Berton, Ilenia Segatto, Linda Fabris, Vincenzo Canzonieri, Alfonso Colombatti, Andrea Vecchione, Barbara Belletti, Gustavo Baldassarre
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e45561 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23029098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Stathmin
• Tumor Suppressor Protein p53

Topics

• Animals
• Base Sequence
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics)
• Gene Expression
• Genes, ras
• Heterozygote
• Mice
• Mice, Knockout
• Neoplasms (genetics, metabolism, mortality, pathology)
• Stathmin (genetics, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)