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Title: Heat induces gene amplification in cancer cells

Abstract

Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Signmore » C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.« less

Authors:
 [1];  [2];  [3];  [1];  [4];  [5];  [1];  [6];  [5]
  1. Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States)
  2. (United States)
  3. Department of Respiratory Medicine, The Second Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410011 (China)
  4. (China)
  5. Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States)
  6. Dermatology, Duke University Medical Center, Durham, NC 27710 (United States)
Publication Date:
OSTI Identifier:
22210302
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 427; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA; DNA REPAIR; DNA REPLICATION; GENE AMPLIFICATION; HYPERTHERMIA; LIGASES; NEOPLASMS; STRAND BREAKS; THERAPY

Citation Formats

Yan, Bin, E-mail: yanbin@mercyhealth.com, Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401, Ouyang, Ruoyun, Huang, Chenghui, Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013, Liu, Franklin, Neill, Daniel, Li, Chuanyuan, and Dewhirst, Mark. Heat induces gene amplification in cancer cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.09.011.
Yan, Bin, E-mail: yanbin@mercyhealth.com, Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401, Ouyang, Ruoyun, Huang, Chenghui, Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013, Liu, Franklin, Neill, Daniel, Li, Chuanyuan, & Dewhirst, Mark. Heat induces gene amplification in cancer cells. United States. doi:10.1016/J.BBRC.2012.09.011.
Yan, Bin, E-mail: yanbin@mercyhealth.com, Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401, Ouyang, Ruoyun, Huang, Chenghui, Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013, Liu, Franklin, Neill, Daniel, Li, Chuanyuan, and Dewhirst, Mark. Fri . "Heat induces gene amplification in cancer cells". United States. doi:10.1016/J.BBRC.2012.09.011.
@article{osti_22210302,
title = {Heat induces gene amplification in cancer cells},
author = {Yan, Bin, E-mail: yanbin@mercyhealth.com and Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401 and Ouyang, Ruoyun and Huang, Chenghui and Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013 and Liu, Franklin and Neill, Daniel and Li, Chuanyuan and Dewhirst, Mark},
abstractNote = {Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.},
doi = {10.1016/J.BBRC.2012.09.011},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 427,
place = {United States},
year = {2012},
month = {10}
}