Journal article
Forkhead Box M1 Regulates Quiescence-Associated Radioresistance of Human Head and Neck Squamous Carcinoma Cells
Radiation research, Vol.182(4), pp.420-429
10/2014
DOI: 10.1667/RR13726.1
PMCID: PMC4221113
PMID: 25229973
Abstract
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% G
1
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) andC-Cmotifligand5 (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.
Details
- Title: Subtitle
- Forkhead Box M1 Regulates Quiescence-Associated Radioresistance of Human Head and Neck Squamous Carcinoma Cells
- Creators
- Jaimee C Eckers - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaAmanda L Kalen - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaEhab H Sarsour - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaVan S Tompkins - Department of Pathology, University of Iowa, Iowa City, IowaSiegfried Janz - Department of Pathology, University of Iowa, Iowa City, IowaJyung Mean Son - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaClaire M Doskey - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaGarry R Buettner - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IowaPrabhat C Goswami - Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.182(4), pp.420-429
- DOI
- 10.1667/RR13726.1
- PMID
- 25229973
- PMCID
- PMC4221113
- NLM abbreviation
- Radiat Res
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Language
- English
- Date published
- 10/2014
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984046822402771
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