PMID- 21324396
OWN - NLM
STAT- MEDLINE
DCOM- 20120706
LR  - 20120410
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 174
IP  - 2
DP  - 2012 May 15
TI  - p53 inhibits vascular endothelial growth factor expression in solid tumor.
PG  - 291-7
LID - 10.1016/j.jss.2010.12.028 [doi]
AB  - BACKGROUND: The p53 tumor-suppressor gene is one of the most frequently mutated 
      genes in cancers, and its mutations affect various biological actions, such as 
      tumor growth, apoptosis, and so on. During hypoxia, p53 is stabilized by 
      interaction with hypoxia-inducible factor-1 (HIF-1). This interaction raised the 
      possibility for regulating HIF-1 activity by p53, which is still to be 
      elucidated. METHODS: First, we introduced various types of the p53 mutant gene 
      into Hep3B and evaluated the role of p53 in hypoxic responses, including vascular 
      endothelial growth factor (VEGF) production and HIF-1 activation. Second, 
      Hep3B-vector cells and Hep3B-p53 cells were subcutaneously injected into BALB/c 
      (nu/nu) mice, and tumor progression and the hypoxic responses were analyzed. 
      Finally, we investigated the role of the p53 mutant genes in the level of 
      vascularity in human pancreatic neoplasia. RESULTS: Here, we showed that 
      expression of wild-type p53, but not null or mutated p53, significantly 
      suppressed HIF-1 activity and production of VEGF, which mostly depends on the 
      HIF-1beta protein level. In a tumor xenograft model, we consistently found that loss 
      of p53 promotes VEGF production, neovascularization, and tumor progression via 
      accumulation of HIF-1beta protein. Furthermore, in clinical pancreatic neoplasia, 
      tumors with mutated p53 have significantly higher levels of vascularity than 
      those with wild-type p53. CONCLUSION: These results indicate that loss of p53 
      contributes to neovascularization through regulation of HIF-1.
CI  - Published by Elsevier Inc.
FAU - Yoshioka, Yasuhiko
AU  - Yoshioka Y
AD  - The Department of Surgery, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
FAU - Shimizu, Shigeomi
AU  - Shimizu S
FAU - Ito, Toshinori
AU  - Ito T
FAU - Taniguchi, Masahiko
AU  - Taniguchi M
FAU - Nomura, Masaya
AU  - Nomura M
FAU - Nishida, Toshirou
AU  - Nishida T
FAU - Sawa, Yoshiki
AU  - Sawa Y
LA  - eng
PT  - Journal Article
DEP - 20110115
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Arnt protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neovascularization, Pathologic
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - Point Mutation
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2011/02/18 06:00
MHDA- 2012/07/07 06:00
CRDT- 2011/02/18 06:00
PHST- 2010/10/23 00:00 [received]
PHST- 2010/12/06 00:00 [revised]
PHST- 2010/12/16 00:00 [accepted]
PHST- 2011/02/18 06:00 [entrez]
PHST- 2011/02/18 06:00 [pubmed]
PHST- 2012/07/07 06:00 [medline]
AID - S0022-4804(10)01892-5 [pii]
AID - 10.1016/j.jss.2010.12.028 [doi]
PST - ppublish
SO  - J Surg Res. 2012 May 15;174(2):291-7. doi: 10.1016/j.jss.2010.12.028. Epub 2011 
      Jan 15.