PMID- 20881962
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20220316
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 468
IP  - 7320
DP  - 2010 Nov 4
TI  - Osteoclast differentiation factor RANKL controls development of progestin-driven 
      mammary cancer.
PG  - 98-102
LID - 10.1038/nature09387 [doi]
AB  - Breast cancer is one of the most common cancers in humans and will on average 
      affect up to one in eight women in their lifetime in the United States and 
      Europe. The Women's Health Initiative and the Million Women Study have shown that 
      hormone replacement therapy is associated with an increased risk of incident and 
      fatal breast cancer. In particular, synthetic progesterone derivatives 
      (progestins) such as medroxyprogesterone acetate (MPA), used in millions of women 
      for hormone replacement therapy and contraceptives, markedly increase the risk of 
      developing breast cancer. Here we show that the in vivo administration of MPA 
      triggers massive induction of the key osteoclast differentiation factor RANKL 
      (receptor activator of NF-kappaB ligand) in mammary-gland epithelial cells. Genetic 
      inactivation of the RANKL receptor RANK in mammary-gland epithelial cells 
      prevents MPA-induced epithelial proliferation, impairs expansion of the CD49f(hi) 
      stem-cell-enriched population, and sensitizes these cells to DNA-damage-induced 
      cell death. Deletion of RANK from the mammary epithelium results in a markedly 
      decreased incidence and delayed onset of MPA-driven mammary cancer. These data 
      show that the RANKL/RANK system controls the incidence and onset of 
      progestin-driven breast cancer.
FAU - Schramek, Daniel
AU  - Schramek D
AD  - IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 
      1030 Vienna, Austria.
FAU - Leibbrandt, Andreas
AU  - Leibbrandt A
FAU - Sigl, Verena
AU  - Sigl V
FAU - Kenner, Lukas
AU  - Kenner L
FAU - Pospisilik, John A
AU  - Pospisilik JA
FAU - Lee, Heather J
AU  - Lee HJ
FAU - Hanada, Reiko
AU  - Hanada R
FAU - Joshi, Purna A
AU  - Joshi PA
FAU - Aliprantis, Antonios
AU  - Aliprantis A
FAU - Glimcher, Laurie
AU  - Glimcher L
FAU - Pasparakis, Manolis
AU  - Pasparakis M
FAU - Khokha, Rama
AU  - Khokha R
FAU - Ormandy, Christopher J
AU  - Ormandy CJ
FAU - Widschwendter, Martin
AU  - Widschwendter M
FAU - Schett, Georg
AU  - Schett G
FAU - Penninger, Josef M
AU  - Penninger JM
LA  - eng
GR  - R01 HD055601/HD/NICHD NIH HHS/United States
GR  - R01 HD055601-04/HD/NICHD NIH HHS/United States
GR  - HD055601/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100929
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Integrin alpha6)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 0 (Progestins)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
SB  - IM
CIN - Nat Rev Cancer. 2010 Nov;10(11):738. PMID: 21080581
CIN - Nat Rev Endocrinol. 2011 Jan;7(1):2. PMID: 21197701
CIN - Breast Cancer Res. 2011;13(1):302. PMID: 21345281
CIN - Breast Cancer Res. 2011;13(1):301. PMID: 21345282
MH  - Animals
MH  - Apoptosis/radiation effects
MH  - Cell Differentiation
MH  - Cell Proliferation/drug effects
MH  - DNA Damage
MH  - Epithelial Cells/cytology/drug effects/metabolism/radiation effects
MH  - Female
MH  - Gamma Rays
MH  - Integrin alpha6/metabolism
MH  - Mammary Neoplasms, Experimental/*chemically 
      induced/genetics/metabolism/*pathology
MH  - Medroxyprogesterone Acetate/administration & dosage/adverse effects
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Osteoclasts/cytology
MH  - Phosphoproteins/analysis/immunology
MH  - Progestins/administration & dosage/*adverse effects
MH  - RANK Ligand/deficiency/genetics/*metabolism
MH  - Receptor Activator of Nuclear Factor-kappa B/deficiency/genetics/metabolism
MH  - Signal Transduction
MH  - Stem Cells/cytology/drug effects/metabolism
PMC - PMC3084017
MID - NIHMS290461
EDAT- 2010/10/01 06:00
MHDA- 2011/01/14 06:00
PMCR- 2011/04/28
CRDT- 2010/10/01 06:00
PHST- 2009/11/09 00:00 [received]
PHST- 2010/07/28 00:00 [accepted]
PHST- 2010/10/01 06:00 [entrez]
PHST- 2010/10/01 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
PHST- 2011/04/28 00:00 [pmc-release]
AID - nature09387 [pii]
AID - 10.1038/nature09387 [doi]
PST - ppublish
SO  - Nature. 2010 Nov 4;468(7320):98-102. doi: 10.1038/nature09387. Epub 2010 Sep 29.