The Phosphoprotein Op18/Stathmin is Differentially Expressed in Ovarian Cancer

Price, Douglas K.; Ball, Jennifer R.; Bahrani-Mostafavi, Zahra; Vachris, Judith C.; Kaufman, Jay S.; Naumann, R. Wendel; Higgins, Robert V.; Hall, James B.

doi:10.3109/07357900009012204

Cited by 77 publications

(74 citation statements)

References 20 publications

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“…This is the first report to provide a possible biophysical explanation for the increased sensitivity to Vinca alkaloids in cells over-expressing stathmin [12]. This mechanism could contribute to Vinca alkaloid selectivity for tumor cells in which stathmin is over-expressed compared to normal cells [7][8][9][10].…”

Section: Biological Significancementioning

confidence: 85%

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Stathmin/Op18 is a novel mediator of vinblastine activity

et al. 2008

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Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary:MINT-6603918: tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027) MINT-6603930: tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065)

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Section: Biological Significancementioning

confidence: 85%

“…A number of reports have shown that stathmin is expressed at high levels in a wide variety of human cancers [7][8][9][10]. Furthermore, it has been observed that stathmin modifies the antimitotic efficiency of antitumor cancer drugs, such as vinblastine (VLB) [11,12].…”

Section: Introductionmentioning

confidence: 99%

Stathmin/Op18 is a novel mediator of vinblastine activity

et al. 2008

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“…54,55 Stathmin is expressed at high levels in a wide variety of human malignancies. [56][57][58][59] We identified overexpression of stathmin in ACC tissue. Further, we detected stathmin protein expression in 2 cases with NSG, 10 cases of PA and 10 cases of ACC using immunohistochemistry (Fig.…”

Section: Figurementioning

confidence: 99%

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands

Nakashima

Uzawa

Kasamatsu

et al. 2005

Intl Journal of Cancer

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Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n 5 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor. ' 2005 Wiley-Liss, Inc.

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“…Poorly differentiated prostate tumor epithelial cells express more stathmin than do differentiated cells (Friedrich et al, 1995). Differentiation-stage-dependent expression of stathmin has also been noted in ovarian cancer (Price et al, 2000).…”

Section: Introductionmentioning

confidence: 92%

“…A gradient of active stathmin levels is necessary, since a balance of MT stabilizing and destabilizing factors are essential for maintenance of cellular functions. Stathmin has been found to be overexpressed in highly proliferative breast cancers and in ovarian cancers, particularly those that are platinum drug-resistant (Bieche et al, 1998;Brattsand, 2000;Curmi et al, 2000;Johnsson et al, 2000;Price et al, 2000). Overexpression of stathmin is also associated with the sensitivity to MT-binding anticancer agents (Alli et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells

2003

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Two paclitaxel(Ptx)-resistant ovarian cancer cell lines, 1A9/Ptx-10 and 1A9/Ptx-22, isolated from the 1A9 cell line (a clone of the A2780 line) by continuous exposure to Ptx and verapamil, have point mutations in their major b-tubulin gene and in one or both alleles of their TP53 gene. These cells were examined for alterations in cell cycle regulators and the tubulin-binding protein stathmin. Unlike parental cells, neither 1A9/Ptx-10 nor 1A9/Ptx-22 expressed detectable levels of p21 WAF1/Cip1 , a putative transcriptional regulator of stathmin, but did overexpress stathmin and Bcl2. No differences were noted in the expression levels of proliferative cell nuclear antigen or tyrosine-phosphorylated p34 Cdc2 . Ptx treatment altered little the expression of stathmin in the parental cell line, although it increased p21 WAF1/Cip1 levels several-fold. Infection of Ptx-resistant lines with a wild-type TP53-bearing adenovirus (AdWTp53) changed cell cycle distribution and increased the levels of p21 WAF1/Cip1 , but caused no changes in stathmin levels. Microtubule drug resistance in ovarian carcinoma may be associated with altered p53/21 WAF1/Cip1 regulatory pathways for stathmin expression and function.

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The Phosphoprotein Op18/Stathmin is Differentially Expressed in Ovarian Cancer

Cited by 77 publications

References 20 publications

Stathmin/Op18 is a novel mediator of vinblastine activity

Stathmin/Op18 is a novel mediator of vinblastine activity

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands

Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells

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