PMID- 27899988
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 12
IP  - 5
DP  - 2016 Nov
TI  - mTOR downstream effectors, 4EBP1 and eIF4E, are overexpressed and associated with 
      HPV status in precancerous lesions and carcinomas of the uterine cervix.
PG  - 3234-3240
AB  - The present study aims to investigate the expression levels of two critical 
      mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 
      (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous 
      squamous intraepithelial lesions and cancer of the uterine cervix, and their 
      association with human papilloma virus (HPV) infection status. Uterine cervical 
      biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 
      archival formalin-fixed, paraffin-embedded tissue specimens. Whole protein 
      extracts were analyzed for the expression of 4EBP1 and eIF4E proteins using 
      western blotting. In addition, distribution of 4EBP1 and eIF4E protein expression 
      and 4EBP1 phosphorylation (P-4EBP1) were analyzed by immunohistochemistry in 
      archival tissues and correlated with the degree of dysplasia. The presence of 
      high-risk HPV (HR-HPV) types was assessed by polymerase chain reaction. Using 
      western blot analysis, high expression levels of 4EBP1 and eIF4E were observed in 
      all uterine cervical carcinomas, which significantly correlated with the degree 
      of dysplasia. By immunohistochemistry, overexpression of 4EBP1 and eIF4E was 
      detected in 20 of 21 (95%) and 17 of 21 (81%) samples, respectively, in patients 
      with high-grade dysplasia and carcinomas, compared with 1 of 20 (5%) and 2 of 20 
      (10%) samples, respectively, in patients with low-grade lesions or normal 
      histology. All 4EBP1-positive cases tested were also positive for P-4EBP1. 
      Furthermore, overexpression of 4EBP1 and eIF4E significantly correlated with the 
      presence of HR-HPV oncogenic types. The present study demonstrated that critical 
      effectors of mTOR signaling, which control protein synthesis initiation, are 
      overexpressed in cervical high-grade dysplasia and cancer, and their levels 
      correlate with oncogenic HPV types. These findings may provide novel targets for 
      investigational therapeutic approaches in patients with cancer of the uterine 
      cervix.
FAU - Asimomytis, Aristidis
AU  - Asimomytis A
AD  - First Department of Pathology, National and Kapodistrian University of Athens, 
      School of Medicine, GR-11527 Athens, Greece.
FAU - Karanikou, Maria
AU  - Karanikou M
AD  - First Department of Pathology, National and Kapodistrian University of Athens, 
      School of Medicine, GR-11527 Athens, Greece.
FAU - Rodolakis, Alexander
AU  - Rodolakis A
AD  - First Department of Obstetrics and Gynecology, National and Kapodistrian 
      University of Athens, Alexandra Maternity Hospital, GR-11528 Athens, Greece.
FAU - Vaiopoulou, Anna
AU  - Vaiopoulou A
AD  - First Department of Pathology, National and Kapodistrian University of Athens, 
      School of Medicine, GR-11527 Athens, Greece.
FAU - Tsetsa, Paraskevi
AU  - Tsetsa P
AD  - First Department of Obstetrics and Gynecology, National and Kapodistrian 
      University of Athens, Alexandra Maternity Hospital, GR-11528 Athens, Greece.
FAU - Creatsas, George
AU  - Creatsas G
AD  - Second Department of Obstetrics and Gynecology, National and Kapodistrian 
      University of Athens, Aretaieion Hospital, GR-11528 Athens, Greece.
FAU - Stefos, Theodoros
AU  - Stefos T
AD  - Department of Obstetrics and Gynecology, University of Ioannina, School of 
      Medicine, GR-45110 Ioannina, Greece.
FAU - Antsaklis, Aristidis
AU  - Antsaklis A
AD  - First Department of Obstetrics and Gynecology, National and Kapodistrian 
      University of Athens, Alexandra Maternity Hospital, GR-11528 Athens, Greece.
FAU - Patsouris, Efstratios
AU  - Patsouris E
AD  - First Department of Pathology, National and Kapodistrian University of Athens, 
      School of Medicine, GR-11527 Athens, Greece.
FAU - Rassidakis, George Z
AU  - Rassidakis GZ
AD  - First Department of Pathology, National and Kapodistrian University of Athens, 
      School of Medicine, GR-11527 Athens, Greece; Department of Pathology and 
      Cytology, Karolinska University Hospital and Karolinska Institute, Solna 17176, 
      Sweden.
LA  - eng
PT  - Journal Article
DEP - 20160829
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5103924
OTO - NOTNLM
OT  - 4EBP1
OT  - Ca
OT  - HG-SIL
OT  - HPV
OT  - LG-SIL
OT  - eIF4E
EDAT- 2016/12/03 06:00
MHDA- 2016/12/03 06:01
PMCR- 2016/08/29
CRDT- 2016/12/01 06:00
PHST- 2015/05/20 00:00 [received]
PHST- 2016/06/07 00:00 [accepted]
PHST- 2016/12/01 06:00 [entrez]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2016/12/03 06:01 [medline]
PHST- 2016/08/29 00:00 [pmc-release]
AID - OL-0-0-5056 [pii]
AID - 10.3892/ol.2016.5056 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 Nov;12(5):3234-3240. doi: 10.3892/ol.2016.5056. Epub 2016 Aug 
      29.