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Title: Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

Abstract

Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 andmore » 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.« less

Authors:
 [1];  [2];  [1];  [1]
  1. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States)
  2. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States)
Publication Date:
OSTI Identifier:
22149536
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 2; 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 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ADOLESCENTS; CARCINOGENS; ESTRADIOL; HEALTH HAZARDS; IONIZING RADIATIONS; MAMMARY GLANDS; MICE; NEOPLASMS; RADIATION DOSES; RADIOTHERAPY; RECEPTORS; URINE

Citation Formats

Suman, Shubhankar, Johnson, Michael D., Fornace, Albert J., Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, and Datta, Kamal. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.12.033.
Suman, Shubhankar, Johnson, Michael D., Fornace, Albert J., Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, & Datta, Kamal. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland. United States. https://doi.org/10.1016/J.IJROBP.2011.12.033
Suman, Shubhankar, Johnson, Michael D., Fornace, Albert J., Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, and Datta, Kamal. 2012. "Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland". United States. https://doi.org/10.1016/J.IJROBP.2011.12.033.
@article{osti_22149536,
title = {Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland},
author = {Suman, Shubhankar and Johnson, Michael D. and Fornace, Albert J. and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC and Datta, Kamal},
abstractNote = {Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.},
doi = {10.1016/J.IJROBP.2011.12.033},
url = {https://www.osti.gov/biblio/22149536}, journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 84,
place = {United States},
year = {Mon Oct 01 00:00:00 EDT 2012},
month = {Mon Oct 01 00:00:00 EDT 2012}
}