RRC ID 34815
著者 Suzuki M, Yamauchi M, Oka Y, Suzuki K, Yamashita S.
タイトル Live-cell imaging visualizes frequent mitotic skipping during senescence-like growth arrest in mammary carcinoma cells exposed to ionizing radiation.
ジャーナル Int J Radiat Oncol Biol Phys
Abstract PURPOSE:Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays.
METHODS AND MATERIALS:Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays.
RESULTS:Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO(2)-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ß-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function.
CONCLUSIONS:The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.
巻・号 83(2)
ページ e241-50
公開日 2012-6-1
DOI 10.1016/j.ijrobp.2011.12.003
PII S0360-3016(11)03658-3
PMID 22365624
MeSH Breast Neoplasms / pathology Breast Neoplasms / physiopathology Breast Neoplasms / radiotherapy* Cell Cycle Proteins / metabolism Cell Line, Tumor Cellular Senescence / physiology* Cyclin E / metabolism Female Fluorescent Antibody Technique / methods G1 Phase / physiology G1 Phase / radiation effects* G2 Phase / physiology G2 Phase / radiation effects* Humans Microscopy, Phase-Contrast / methods Mitosis / physiology Mitosis / radiation effects* RNA, Small Interfering / metabolism Radiation Dosage Time Factors Tumor Suppressor Protein p53 / metabolism* beta-Galactosidase / metabolism
IF 5.859
引用数 6
WOS 分野 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING ONCOLOGY
リソース情報
遺伝子材料 pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) CSII-CMV-MCS-IRES2-Bsd (RDB04385).