Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Effects of iron deficiency and iron overload on angiogenesis and oxidative stress-a potential dual role for iron in breast cancer.

Authors: Jian, Jinlong; Yang, Qing; Dai, Jisen; Eckard, Jonathan; Axelrod, Deborah; Axelrod, Debrah; Smith, Julia; Huang, Xi

Published In Free Radic Biol Med, (2011 Apr 1)

Abstract: Estrogen alone cannot explain the differences in breast cancer (BC) recurrence and incidence rates in pre- and postmenopausal women. In this study, we have tested a hypothesis that, in addition to estrogen, both iron deficiency due to menstruation and iron accumulation as a result of menstrual stop play important roles in menopause-related BC outcomes. We first tested this hypothesis in cell culture models mimicking the high-estrogen and low-iron premenopausal condition or the low-estrogen and high-iron postmenopausal condition. Subsequently, we examined this hypothesis in mice that were fed iron-deficient and iron-overloaded diets. We show that estrogen only slightly up-regulates vascular endothelial growth factor (VEGF), an angiogenic factor known to be important in BC recurrence. It is, rather, iron deficiency that significantly promotes VEGF by stabilizing hypoxia-inducible factor-1ýý. Conversely, high iron levels increase oxidative stress and sustain mitogen-activated protein kinase activation, which are mechanisms of known significance in BC development. Taken together, our results suggest, for the first time, that an iron-deficiency-mediated proangiogenic environment could contribute to the high recurrence of BC in young patients, and iron-accumulation-associated pro-oxidant conditions could lead to the high incidence of BC in older women.

PubMed ID: 21193031 Exiting the NIEHS site

MeSH Terms: Anemia, Iron-Deficiency/complications; Anemia, Iron-Deficiency/metabolism; Animals; Breast Neoplasms/etiology; Breast Neoplasms/metabolism; Breast Neoplasms/physiopathology; Cell Line, Tumor; Estrogens/metabolism; Estrogens/pharmacology*; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/genetics; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Iron Overload/complications; Iron Overload/metabolism*; Iron, Dietary/metabolism*; Iron/metabolism*; Iron/pharmacology; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases/genetics; Mitogen-Activated Protein Kinases/metabolism*; Neovascularization, Pathologic/complications; Neovascularization, Pathologic/metabolism; Oxidative Stress/drug effects; Postmenopause/metabolism; Premenopause/metabolism; Transcriptional Activation/drug effects; Up-Regulation; Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism*

Back
to Top