Expression of Cell Cycle Regulatory Proteins on the Solid Tumor Cell Line After Irradiation Under Hypoxia.
- Author:
Kyung Ah PARK
1
;
Yoon Jung CHOI
;
Eun Jung CHOI
;
Hye Jin HWANG
;
Yong Woo LEE
;
Won Taek LEE
;
Jong Eun LEE
Author Information
1. Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. jelee@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Irradiation;
Hypoxia;
NIH3T3 cell;
MCF7 cell;
HepG2 cell;
apoptosis
- MeSH:
Anoxia*;
Apoptosis;
Breast Neoplasms;
Carcinoma, Hepatocellular;
Cell Cycle Checkpoints;
Cell Cycle Proteins*;
Cell Cycle*;
Cell Death;
Cell Line;
Cell Line, Tumor*;
DNA;
DNA Damage;
DNA Fragmentation;
Drug Therapy;
Electrophoresis;
Hep G2 Cells;
Humans;
MCF-7 Cells;
Oxygen;
Radiation Tolerance;
Radiotherapy
- From:Korean Journal of Anatomy
2005;38(6):567-578
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Human solid tumors are less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy. Many of genes encoding proteins induced by hypoxia are potential products for modifying the radiation response of normal or malignant tissues. Radiosensitivity or radioresisitance of the solid tumor cell lines can be exploited in overcoming the resistance to radiotherapy for cancer treatment. In this study, we investigated the radiosensitivity or radioresistance of the solid tumor cell line induced by hypoxia after radiation and the effect of hypoxia or/and irradiation on the expression of cell cycle regulatory proteins in the NIH3T3, MCF7 and HepG2 cell line. In normal cell line, NIH3T3, the cell death induced by irradiation was decreased by undergoing hypoxic treatment before radiation in the FACS and LDH assays. The percentage of cell death resulted in a significant increase by 70~80% in the NIH3T3 and HepG2 cell line after irradiation or hypoxia, but the cell death was significantly decreased after irradation under hypoxia in the HepG2 cells. However there is no difference in the cell death of MCF7 cells after same insults. DNA fragmentation was observed in only HepG2 cells under hypoxia by Heochst-PI nuclear staining, DNA gel electrophoresis and FACS analysis. In human breast cancer cell line MCF7, the level of E2F was more increased in hypoxia than normoxia, but was decreased after gamma-irradiation. However, it was shown that the effects of radiation can be changed by reoxygenation condition after hypoxia in human hepatoma cell line HepG2. The expression of E2F-1 was observed to decrease in HepG2 when cells were exposed to gamma-radiation after hypoxia. While investigating in MCF7 cells, the level of E2F-1 was increased under hypoxia. However, the expression of p53 decreased in hypoxia, though was increased after irradiation in the NIH3T3, MCF7 and HepG2 cell line. The increase of E2F-1 expression in MCF7 cells may be associated with hypoxic resistance in hypoxia-mediated apoptosis of tumors. The level of E2F may contribute to some critical factors of cellular repair function associated with DNA damage, and to deciding whether the cells will pass through cell cycle arrest or apoptosis.
