Stathmin is overexpressed in malignant mesothelioma

Thoracic Oncology Laboratory, UCSF Comprehensive Cancer Center, San Francisco, CA 94115, USA.
Anticancer research (Impact Factor: 1.83). 01/2007; 27(1A):39-44. DOI: 10.3161/068.042.0111
Source: PubMed


Malignant pleural mesothelioma is a highly aggressive cancer, with low overall survival. The pathogenesis of mesothelioma is poorly understood. The aim of this study was to identify potential genes overexpressed in mesothelioma.
A cDNA microarray was used to identify potential genes that are activated in mesothelioma cell lines. Overexpression of stathmin, a cytosolic protein that regulates microtubule dynamics, was found. RT-PCR, Western blot, and immunohistochemistry were used to confirm overexpression in both cell lines and tumor samples.
Using RT-PCR and Western blot, stathmin overexpression was confirmed in seven mesothelioma cell lines. Increased stathmin protein expression was also found in seven out of eight mesothelioma tumor samples. Finally, stathmin expression in a mesothelioma tumor was confirmed by immunohistochemistry.
For the first time, stathmin was shown to be overexpressed in malignant mesothelioma. The overexpression of stathmin in mesothelioma may offer a potential therapeutic target and further studies are warranted.

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Available from: Jae Y Kim, Nov 18, 2014
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    • "Stathmin1 (STMN1), also known as oncoprotein 18, is an important cytosolic microtubule-destabilizing protein which plays critical role in the process of mitosis through regulation of microtubule dynamics, and a variety of other biological processes [10]. High level of STMN1 expression is associated with poor prognosis in various malignancies including breast cancer [11], [12], prostate cancer [13], malignant mesothelioma [14], cervical cancer [15], and esophageal squamous cell carcinoma [16]. In 2010, Jeon et al. first reported that STMN1 over-expression was positively correlated with lymph node metastasis and advanced staging and vascular invasion, and negatively with recurrence-free survival in diffuse type gastric carcinoma [17]. "
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    ABSTRACT: Stathmin1 (STMN1) is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age (p = 0.043), T stage (p = 0.004) and lymph node metastasis (p = 0.046). Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis (p = 0.01). STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation (p<0.001), reduced monolayer colony formation (p<0.001), inhibited cell invasion and migration ability (p<0.001) and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo (p<0. 01). We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.
    Full-text · Article · Mar 2012 · PLoS ONE
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    ABSTRACT: Mesothelioma is a rare malignancy arising from mesothelial cells lining the pleura and peritoneum. Advances in modern technology have allowed the development of array based approaches to the study of disease allowing researchers the opportunity to study many genes or proteins in a high-throughput fashion. This review describes the current knowledge surrounding array based approaches with respect to mesothelioma research.
    Full-text · Article · Apr 2009 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: To construct a eukaryotic expression vector of stathmin gene and investigate its effect on esophageal squamous cell carcinoma (ESCC) EC9706 cell line. Stathmin cDNA coding sequence was amplified by RT-PCR and cloned into a eukaryotic expression vector pcDNA3.1(+). EC9706 cells were transfected with this recombinant plasmid pcDNA3.1-stathmin by lipofectamine. And the stable transfectants were selected with G418 medium. Stathmin protein expression was detected with Western blot in transfected EC9706 cell lines. Morphologic change of stable transfectants was observed under microscope. The proliferation of transfected cells was measured by cell counting, MTT and in vitro formation assay of flat. Flow cytometry was used to detect the cell cycle. Nude mice were adopted to investigate the in vivo tumorigenic characteristics of the transfected cells. A 450 bp coding sequence of stathmin cDNA was amplified by RT-PCR and then cloned into pcDNA3.1(+) plasmid to harvest the recombinant plasmid pcDNA3.1-stathmin. The recombinant plasmid pcDNA3.1-stathmin and blank vector were transfected respectively into EC9706 cells. The up-regulated expression of stathmin protein was validated by Western blot (P < 0.01). Compared with control, EC9706 cells transfected with pcDNA3.1-stathmin appeared swollen and multi-nuclear with a cell mitotic arrest; doubling generation time of pcDNA3.1-stathmin transfectants was prolonged (25 - 28 h); The in vitro cell proliferation ability and clone formation rate (34.5% ± 6.9%) decreased, cell cleavage was blocked at G(2)/M phase (21.7% ± 3.4%) and the oncogenicity of inoculated cells in nude mice decreased (all P < 0.01). The up-regulated expression of stathmin protein triggered by the recombinant plasmid pcDNA3.1-stathmin can inhibit the proliferation and oncogenicity of ESCC EC9706 cells. This molecule may be a promising therapeutic target in ESCC patients.
    No preview · Article · Aug 2010 · Zhonghua yi xue za zhi
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