PMID- 20498644
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20220330
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 27
DP  - 2010 Jul 8
TI  - Pdcd4 repression of lysyl oxidase inhibits hypoxia-induced breast cancer cell 
      invasion.
PG  - 3921-32
LID - 10.1038/onc.2010.158 [doi]
AB  - Metastasis to bone, liver and lungs is the primary cause of death in breast 
      cancer patients. Our studies have revealed that the novel tumor suppressor Pdcd4 
      inhibits breast cancer cell migration and invasion in vitro. Loss of Pdcd4 in 
      human nonmetastatic breast cancer cells increased the expression of lysyl oxidase 
      (LOX) mRNA. LOX is a hypoxia-inducible amine oxidase, the activity of which 
      enhances breast cancer cell invasion in vitro and in vivo. Specific inhibition of 
      LOX activity by beta-aminopropionitrile or small interfering RNA decreased the 
      invasiveness of T47D and MCF7 breast cancer cells attenuated for Pdcd4 function. 
      Most significantly, loss of Pdcd4 augments hypoxia induction of LOX as well. 
      Conversely, overexpression of Pdcd4 significantly reversed the hypoxia induction 
      of LOX expression in T47D cells attenuated for Pdcd4. However, Pdcd4 did not 
      affect hypoxia-inducible factor-1 (HIF-1) protein expression or HIF-1-responsive 
      element-luciferase activity in response to hypoxia, suggesting that Pdcd4 
      regulation of LOX occurs through an HIF-independent mechanism. Nevertheless, the 
      loss of Pdcd4 early in cancer progression may have an important role in the 
      increased sensitivity of cancer cells to hypoxia through increased LOX activity 
      and concomitant enhanced invasiveness.
FAU - Santhanam, A N
AU  - Santhanam AN
AD  - Gene Regulation Section, Laboratory of Cancer Prevention, Center for Cancer 
      Research, National Cancer Institute, Frederick, MD 21702, USA. 
      santhanama@ncifcrf.gov
FAU - Baker, A R
AU  - Baker AR
FAU - Hegamyer, G
AU  - Hegamyer G
FAU - Kirschmann, D A
AU  - Kirschmann DA
FAU - Colburn, N H
AU  - Colburn NH
LA  - eng
GR  - ZIA BC010026-15/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20100524
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Drug Combinations)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Laminin)
RN  - 0 (PDCD4 protein, human)
RN  - 0 (Proteoglycans)
RN  - 0 (RNA-Binding Proteins)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
SB  - IM
MH  - Apoptosis Regulatory Proteins/deficiency/genetics/*metabolism
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Collagen/metabolism
MH  - Drug Combinations
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Laminin/metabolism
MH  - Neoplasm Invasiveness/genetics
MH  - Protein-Lysine 6-Oxidase/genetics/*metabolism
MH  - Proteoglycans/metabolism
MH  - RNA-Binding Proteins/genetics/*metabolism
PMC - PMC3419530
MID - NIHMS388768
COIS- Conflict of interest The authors declare no conflict of interest.
EDAT- 2010/05/26 06:00
MHDA- 2010/07/31 06:00
PMCR- 2012/08/15
CRDT- 2010/05/26 06:00
PHST- 2010/05/26 06:00 [entrez]
PHST- 2010/05/26 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2012/08/15 00:00 [pmc-release]
AID - onc2010158 [pii]
AID - 10.1038/onc.2010.158 [doi]
PST - ppublish
SO  - Oncogene. 2010 Jul 8;29(27):3921-32. doi: 10.1038/onc.2010.158. Epub 2010 May 24.