Increased Tumorigenicity and Sensitivity to Ionizing Radiation upon Loss of Chromosomal Protein HMGN1
| Autor: | Takashi Furusawa, Katherine L. West, Marta Prymakowska-Bosak, Yehudit Birger, Frédéric Catez, Michael Bustin, Diana C. Haines, Yuri V. Postnikov, Jae-Hwan Lim |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
G2 Phase
Male HMGN1 Cancer Research Neoplasms Radiation-Induced Cell division Mutant Mice Nude HMGN Proteins Radiation Tolerance Article Ionizing radiation Mice 03 medical and health sciences 0302 clinical medicine Animals Radiosensitivity 030304 developmental biology 0303 health sciences biology HMGN Fibroblasts Chromatin Cell Transformation Neoplastic Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Female Cell Division HMGN1 Protein |
| Zdroj: | Cancer Research. 65:6711-6718 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-0310 |
| Popis: | We report that loss of HMGN1, a nucleosome-binding protein that alters the compaction of the chromatin fiber, increases the cellular sensitivity to ionizing radiation and the tumor burden of mice. The mortality and tumor burden of ionizing radiation–treated Hmgn1−/− mice is higher than that of their Hmgn1+/+ littermates. Hmgn1−/− fibroblasts have an altered G2-M checkpoint activation and are hypersensitive to ionizing radiation. The ionizing radiation hypersensitivity and the aberrant G2-M checkpoint activation of Hmgn1−/− fibroblasts can be reverted by transfections with plasmids expressing wild-type HMGN1, but not with plasmids expressing mutant HMGN proteins that do not bind to chromatin. Transformed Hmgn1−/− fibroblasts grow in soft agar and produce tumors in nude mice with a significantly higher efficiency than Hmgn1+/+ fibroblasts, suggesting that loss of HMGN1 protein disrupts cellular events controlling proliferation and growth. Hmgn1−/− mice have a higher incidence of multiple malignant tumors and metastases than their Hmgn1+/+ littermates. We suggest that HMGN1 optimizes the cellular response to ionizing radiation and to other tumorigenic events; therefore, loss of this protein increases the tumor burden in mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|