抗辐射性
生物
基因敲除
头颈部鳞状细胞癌
辐射敏感性
癌症研究
细胞生长
福克斯M1
细胞周期
下调和上调
细胞
分子生物学
细胞生物学
细胞培养
细胞凋亡
癌症
内科学
放射治疗
头颈部癌
基因
医学
生物化学
遗传学
作者
Jaimee C. Eckers,Amanda L. Kalen,Ehab H. Sarsour,Van S. Tompkins,Siegfried Janz,Jyung Mean Son,Claire M. Doskey,Garry R. Buettner,Prabhat C. Goswami
出处
期刊:Radiation Research
[BioOne (Radiation Research Society)]
日期:2014-09-17
卷期号:182 (4): 420-420
被引量:20
摘要
Cellular quiescence is a reversible growth arrest in which cells retain their ability to enter into and exit from the proliferative cycle. This study investigates the hypothesis that cell growth-state specific oxidative stress response regulates radiosensitivity of cancer cells. Results showed that quiescent (low proliferative index; >75% G1 phase and lower RNA content) Cal27 and FaDu human head and neck squamous cell carcinoma (HNSCC) are radioresistant compared to proliferating cells. Quiescent cells exhibited a three to tenfold increase in mRNA levels of Mn-superoxide dismutase (MnSOD), dual oxidase 2 (DUOX2) and dual-specificity phosphatase 1 (DUSP1), while mRNA levels of catalase (CAT), peroxiredoxin 3 (PRDX3) and C-C motif ligand 5 (CCL5) were approximately two to threefold lower compared to proliferating cells. mRNA levels of forkhead box M1 (FOXM1) showed the largest decrease in quiescent cells at approximately 18-fold. Surprisingly, radiation treatment resulted in a distinct gene expression pattern that is specific to proliferating and quiescent cells. Specifically, FOXM1 expression increased two to threefold in irradiated quiescent cells, while the same treatment had no net effect on FOXM1 mRNA expression in proliferating cells. RNA interference and pharmacological-based downregulation of FOXM1 abrogated radioresistance of quiescent cells. Furthermore, radioresistance of quiescent cells was associated with an increase in glucose consumption and expression of glucose-6-phosphate dehydrogenase (G6PD). Knockdown of FOXM1 resulted in a significant decrease in G6PD expression, and pharmacological-inhibition of G6PD sensitized quiescent cells to radiation. Taken together, these results suggest that targeting FOXM1 may overcome radioresistance of quiescent HNSCC.
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