PMID- 30020826
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20211204
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 315
IP  - 4
DP  - 2018 Oct 1
TI  - Acute iodine deficiency induces a transient VEGF-dependent microvascular response 
      in mammary glands involving HIF-1, ROS, and mTOR.
PG  - C544-C557
LID - 10.1152/ajpcell.00095.2017 [doi]
AB  - Iodine deficiency (ID), which affects almost two billion people worldwide, is 
      associated with breast pathologies such as fibrosis in human and induces breast 
      atypia in animal models. Because ID induces vascular activation in the thyroid, 
      another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to 
      characterize ID-induced effects on the breast microvasculature in vivo and in two 
      different breast cell lines in vitro. Virgin and lactating NMRI mice received an 
      iodide-deficient diet and a Na(+)/I(-) symporter inhibitor for 1 to 20 days. Some 
      virgin mice were treated with vascular endothelial growth factor A (VEGF) or VEGF 
      receptor inhibitors. In vitro, ID was induced in MCF7 and MCF12A cells by 
      replacing the iodide-containing medium by an iodide-deficient medium. In vivo, 
      VEGF expression was increased following ID in mammary tissues. Consequently, ID 
      induced a transient increase in mammary gland blood flow, measured after 
      anesthesia, in virgin and lactating mice, which was repressed by VEGF or VEGF 
      receptor inhibitors. In MCF7 cells, ID induced a transient increase in reactive 
      oxygen species, followed by an increase in hypoxia-inducible factor-1alpha (HIF-1alpha) 
      protein and VEGF mRNA expression. Antioxidant N-acetylcysteine and mammalian 
      target of rapamycin (mTOR) inhibitor blocked ID-induced HIF-1alpha protein increase 
      and VEGF transcription. However, mTOR activity was not inhibited by 
      N-acetylcysteine. Similar responses were observed in MCF12A cells. These data 
      indicate that ID activates the canonical VEGF pathway and mTOR in breast tissues, 
      which provides new insights to better understand the correlation between ID, 
      vascular activation, and breast pathologies.
FAU - Vanderstraeten, Jessica
AU  - Vanderstraeten J
AD  - Pole of Morphology, Institut de Recherche Experimentale et Clinique, Universite 
      catholique de Louvain , Brussels , Belgium.
FAU - Derradji, Hanane
AU  - Derradji H
AD  - Radiobiology Unit, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium.
FAU - Sonveaux, Pierre
AU  - Sonveaux P
AD  - Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et 
      Clinique, Universite catholique de Louvain , Brussels , Belgium.
FAU - Colin, Ides M
AU  - Colin IM
AD  - Service d'Endocrino-Diabetologie, Centre Hospitalier Regional, Mons-Hainaut, 
      Belgium.
FAU - Many, Marie-Christine
AU  - Many MC
AD  - Pole of Morphology, Institut de Recherche Experimentale et Clinique, Universite 
      catholique de Louvain , Brussels , Belgium.
FAU - Gerard, Anne-Catherine
AU  - Gerard AC
AD  - Service d'Endocrino-Diabetologie, Centre Hospitalier Regional, Mons-Hainaut, 
      Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180718
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antioxidants)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9679TC07X4 (Iodine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Breast/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Iodine/*deficiency
MH  - Lactation/metabolism
MH  - MCF-7 Cells
MH  - Mammary Glands, Animal/metabolism
MH  - Mammary Glands, Human/*metabolism
MH  - Mice
MH  - Microvessels/*metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, Vascular Endothelial Growth Factor/metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Vascular Endothelial Growth Factor A/*metabolism
OTO - NOTNLM
OT  - breast epithelial cells
OT  - iodine deficiency
OT  - mammalian target of rapamycin
OT  - reactive oxygen species
OT  - vascular endothelial growth factor
EDAT- 2018/07/19 06:00
MHDA- 2019/07/02 06:00
CRDT- 2018/07/19 06:00
PHST- 2018/07/19 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2018/07/19 06:00 [entrez]
AID - 10.1152/ajpcell.00095.2017 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2018 Oct 1;315(4):C544-C557. doi: 
      10.1152/ajpcell.00095.2017. Epub 2018 Jul 18.