Abstract
Objective
To study the effect of X-radiation on expression of hMSH2 and hMLH1 in nasopharyngeal carcinoma (NPC) CNE-1 cells, and explore the mechanism of DNA mismatch repair after radiation.
Methods
The cells were divided into experimental and control groups. Experimental cells were exposed to 10 Gy radiation administered as 2 Gyper fraction. Control cells were not radiated. The distribution of cells in the cell cycle was analyzed using flow cytometry. The expression of hMSH2 and hMLH1 was examined by RT-PCR and Western blots.
Results
The expression of hMSH2 mRNA in experimental cells was significantly greater compared to control cells at 0–3rd weeks and decreased at the 4th week following radiation (P<0.01 ). The expression of hMSH2 protein in experimental cells was up-regulated and significantly greater compared to control cells at the 2nd∼4th weeks after radiation (P<0.01 ). There were no significant differences in hMLH1 mRNA and protein expression between ex perimental and control cells (P>0.05).
Conclusion
Radiation induces hMSH2 expression; hMSH2 has a role in the process of DNA repair, which maybe responsible for reduction of radiosensitivity after radiation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Peltomaki P. Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet. 2001;10: 735–740.
Kolodner RD. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends Biochem Sci. 1995;20:397–401.
Palombo F, Gallinari P, Iaccarino I, et al. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science. 1995; 268:1912–1914.
Drummond JT, Li GM, Longley MJ, et al. Isolation of an hMSH2-pl60 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995; 268:1909–1912.
Palombo F, Iaccarino I, Nakajima E, et al. hMutSbeta, a heterodimer of hMSH2 and hMSH3, binds to insertion/deletion loops in DNA. Curr Biol. 1996; 6:1181–1184.
Leung WK, Kim JJ, Wu L, et al. Identification of a second MutL DNA mismatch repair complex (hPMSl and hMLHl) in human epithelial cells. J Biol Chem. 2000;275: 15728–15732.
Li GM, Modrich P. Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc Natl Acad Sci USA. 1995;92: 1950–1954.
Raschle M, Marra G, Nystrom-Lahti M, et al. Identification of hMutLbeta, a heterodimer of hMLHl and hPMSl. J Biol Chem. 1999; 274: 32368–32375.
Lipkin SM, Wang V, Jacoby R, et al. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet. 2000;24:27–25.
Parsons R, Li GM, Longley MJ, et al. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993; 75:1227–1236.
Eshleman JR, Markowitz SD. Mismatch repair defects in human carcinogenesis. Hum Mol Genet. 1996;5:1489–1494.
Kuraguchi M, Yang K, Wong E, et al. The distinct spectra of tumor-associated Apc mutations in mismatch repair-deficient Apc l638N mice define the roles of MSH3 and MSH6 in DNA repair and intestinal tumorigenesis. Cancer Res. 2001; 61: 7934–7942.
Lynch HT, Smyrk TC, Waston P, et al. Genetic natural history, tumor spectrum, and pathology of herediatary nonpolyposis colorectal cancer: an updated review. Gastroenterology. 1993;104:1535–1549.
Kakar S, Burgart LJ, Thibodeau SN, et al. Frequency of loss of hMLHl expression in colorectal carcinoma increases with advancing age. Cancer. 2003;24:27–35.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by Chinese Scientific Academy Creative Foundation (No. DIPCK2001A4).
About this article
Cite this article
Fan, K., Wang, H., Yu, Z. et al. Changes of hMSH2 and hMLH1 Expression in Nasopharyngeal carcinoma cells after X-radiation. Chin. J. Clin. Oncol. 2, 700–705 (2005). https://doi.org/10.1007/BF02819535
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02819535