PMID- 24184801
OWN - NLM
STAT- MEDLINE
DCOM- 20150420
LR  - 20211203
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 14
IP  - 12
DP  - 2013 Dec
TI  - Dysregulation of the mTOR pathway in p53-deficient mice.
PG  - 1182-8
LID - 10.4161/cbt.26947 [doi]
AB  - Mammalian or mechanistic target of rapamycin (mTOR) is involved in growth, aging, 
      and age-related diseases including cancer. There is an extensive cross talk 
      between p53 and mTOR. In cell culture, p53 inhibits the mTOR pathway in a cell 
      type-dependent manner. p53-deficient mice develop pro-inflammation and cancer. We 
      have shown that rapamycin delayed cancer and extended lifespan, thus partially 
      substituting for p53. Here we show that a marker of mTOR activity, phosphorylated 
      S6 (p-S6), is increased in the hearts of p53-deficient mice. Furthermore, cardiac 
      p-S6 correlated with body weight. Also, p53(-/-) mice were slightly 
      hyperinsulinemic with a tendency to elevated IGF-1. Radiation exacerbated the 
      difference between IGF-1 levels in normal and p53(-/-) mice. Noteworthy, 
      radiation induced Thr-308 Akt phosphorylation in the livers (but not in the 
      hearts) of both p53(+/+) and p53(-/-) mice. Simultaneously, radiation decreased 
      p-S6 in the livers of normal mice, consistent with the negative effect of p53 on 
      mTOR. Our data indicate that the activity of mTOR is increased in some but not 
      all tissues of p53(-/-) mice, associated with the tendency to increased insulin 
      and IGF-1 levels. Therefore, the absence of p53 may create oncophilic 
      microenvironment, favoring cancer.
FAU - Leontieva, Olga V
AU  - Leontieva OV
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
FAU - Novototskaya, Liliya R
AU  - Novototskaya LR
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
FAU - Paszkiewicz, Geraldine M
AU  - Paszkiewicz GM
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
FAU - Komarova, Elena A
AU  - Komarova EA
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
FAU - Gudkov, Andrei V
AU  - Gudkov AV
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
FAU - Blagosklonny, Mikhail V
AU  - Blagosklonny MV
AD  - Department of Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY 
      USA.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20131101
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Liver/metabolism
MH  - Mice, Knockout
MH  - Myocardium/metabolism
MH  - Organ Specificity
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, IGF Type 1/genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tumor Suppressor Protein p53/*genetics
PMC - PMC3912042
OTO - NOTNLM
OT  - aging
OT  - cancer
OT  - inflammation
OT  - mTOR
OT  - p53
OT  - rapalog
OT  - rapamycin
OT  - senescence
EDAT- 2013/11/05 06:00
MHDA- 2015/04/22 06:00
PMCR- 2014/12/01
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 26947 [pii]
AID - 2013CBT6729R [pii]
AID - 10.4161/cbt.26947 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2013 Dec;14(12):1182-8. doi: 10.4161/cbt.26947. Epub 2013 Nov 
      1.