Impact of hypoxia inducible factors on estrogen receptor expression in breast cancer cells.
In women breast cancer is still the most commonly diagnosed cancer. This type of cancer is classified as a hormone-dependent tumor. Estrogen receptor (ER) expression and functional status contribute to breast cancer development and progression. Another important factor associated with cancer is hypoxia which is defined as the state of reduced oxygen availability in tissues. Intratumoral hypoxia results in the activation of the hypoxia inducible factors (HIFs). HIFs are heterodimeric transcription factors involved in the regulation of many cellular processes, such as angiogenesis, anaerobic metabolism, cell proliferation/survival, and promotion of metastasis. In this study we evaluated the interplay between hypoxia, HIF stabilization and the ER-α/β-ratio in several ER-positive breast cancer cell lines. Hypoxia was shown to inhibit ER expression in ER-positive breast cancer cells. Further experiments using the hypoxia mimetic CoCl2and HIF-1α knockdown cells indicated that the influence of hypoxia on breast cancer cells involves other pathways than the molecular oxygen sensing pathway. Moreover, we demonstrated that MCF-7 cells in long-term culture lost part of their ability to respond to hypoxic incubation. Understanding the relationships between HIF, ER-α and ER-β expression holds the promise of the development of new therapeutic agents and may provide future advances in prognosis.
Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Germany; Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany.
Matthias
M
Wolff
Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Germany.
Friederike Katharina
FK
Kosyna
Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany.
Jürgen
J
Dunst
Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Germany.
Wolfgang
W
Jelkmann
Institute of Physiology, Center for Structural and Cell Biology in Medicine, University of Lübeck, Germany. Electronic address: reinhard.depping@uni-luebeck.de.
Reinhard
R
Depping
D001943:Breast Neoplasms / Q000378:metabolism*; D003035:Cobalt / Q000737:chemistry; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D061986:MCF-7 Cells; D010100:Oxygen / Q000737:chemistry
C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; C018021:cobaltous chloride; D010100:Oxygen
Breast cancer; Estrogen receptor (ER); Hypoxia; Hypoxia inducible factor (HIF); Hypoxia mimetics