The 1p-Encoded Protein Stathmin and Resistance of Malignant Gliomas to Nitrosoureas
| Autor: | Xing-Jie Liang, Yuri Kotliarov, Peter McL. Black, Patrick Y. Wen, Dragan Maric, Oluwaseun Akeju, Umberto De Girolami, Wells W. Wu, John K. Park, Jean C. Zenklusen, Teri T.B. Ngo, Wei Zhang, Tien Peng, Neal Jeffries, Sandra Pastorino, Rong Fong Shen, Dong Won Kang, Howard A. Fine |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Nitrosourea Vincristine Molecular Sequence Data Oligodendroglioma Antineoplastic Agents Stathmin Biology Nitrosourea Compounds Loss of heterozygosity chemistry.chemical_compound In vivo Cell Line Tumor Glioma medicine Humans Neoplasm Electrophoresis Gel Two-Dimensional RNA Neoplasm In Situ Hybridization Fluorescence DNA Primers Base Sequence Brain Neoplasms Chromosome Mapping DNA Neoplasm medicine.disease Oncology chemistry Chromosomes Human Pair 1 Drug Resistance Neoplasm biology.protein Cancer research Immunohistochemistry medicine.drug |
| Zdroj: | JNCI Journal of the National Cancer Institute. 99:639-652 |
| ISSN: | 1460-2105 0027-8874 |
| Popis: | Background Malignant gliomas are generally resistant to all conventional therapies. Notable exceptions are anaplastic oligodendrogliomas with loss of heterozygosity on chromosome 1 p (1p +/- ). Patients with 1p +/- anaplastic oligodendroglioma frequently respond to procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine. Because the underlying biologic basis for this clinical finding is unclear, we evaluated differentially expressed 1 p-encoded proteins in 1p +/- and 1p +/+ malignant glioma cell lines and then examined whether their expression was associated with outcome of patients with anaplastic oligodendroglioma. Methods We used a comparative proteomic screen of A172 (1p +/- ) and U251 (1p +/+ ) malignant glioma cell lines to identify differentially expressed 1p-encoded proteins, including stathmin, a microtubule-associated protein. 1p +/- and 1p +/+ anaplastic oligodendroglioma specimens from 24 patients were assessed for stathmin expression by immunohistochemistry. The relationship between stathmin expression and clinical outcome was assessed with Kaplan-Meier analyses. RNA inhibition and cDNA transfection experiments tested effects of stathmin under- and overexpression, respectively, on the in vitro and in vivo resistance of malignant glioma cells to treatment with nitrosourea. For in vivo resistance studies, 36 mice with intracranial and 16 mice with subcutaneous xenograft tumor implants were used (one tumor per mouse). Flow cytometry was used for cell cycle analysis. Immunoblotting was used to assess protein expression. All statistical tests were two-sided. Results Decreased stathmin expression in tumors was statistically significantly associated with loss of heterozygosity in 1p (P |
| Databáze: | OpenAIRE |
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