PMID- 21062985
OWN - NLM
STAT- MEDLINE
DCOM- 20110207
LR  - 20211203
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 22
DP  - 2010 Nov 15
TI  - Mammalian target of rapamycin-dependent acinar cell neoplasia after inactivation 
      of Apc and Pten in the mouse salivary gland: implications for human acinic cell 
      carcinoma.
PG  - 9143-52
LID - 10.1158/0008-5472.CAN-10-1758 [doi]
AB  - Cross-talk between the canonical Wnt and mammalian target of rapamycin (mTOR) 
      signaling pathways occurs at multiple levels in the cell and likely contributes 
      to the oncogenic effects of these pathways in human cancer. To gain more insight 
      into the interplay between Wnt and mTOR signaling in salivary gland 
      tumorigenesis, we developed a mouse model in which both pathways are 
      constitutively activated by the conditional inactivation of the Apc and Pten 
      tumor suppressor genes. Loss of either Apc or Pten alone did not cause tumor 
      development. However, deletion of both genes resulted in the formation of 
      salivary gland tumors with 100% penetrance and short latency that showed a 
      remarkable morphologic similarity to human acinic cell carcinoma. Treatment of 
      tumor-bearing mice using the mTOR inhibitor rapamycin led to complete regression 
      of tumors, indicating that tumor growth was dependent on continued mTOR 
      signaling. Importantly, we found that human salivary gland acinic cell carcinomas 
      also express markers of activated mTOR signaling. Together, these results suggest 
      that aberrant activation of mTOR signaling plays a pivotal role in acinar cell 
      neoplasia of the salivary gland. Because rapamycin analogues are approved for 
      treating other types of human malignancies, our findings suggest that rapamycin 
      therapy should be evaluated for treating patients with salivary gland acinic cell 
      carcinoma.
CI  - Copyright (c) 2010 AACR.
FAU - Diegel, Cassandra R
AU  - Diegel CR
AD  - Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 
      Grand Rapids, Michigan 49504, USA.
FAU - Cho, Kathleen R
AU  - Cho KR
FAU - El-Naggar, Adel K
AU  - El-Naggar AK
FAU - Williams, Bart O
AU  - Williams BO
FAU - Lindvall, Charlotta
AU  - Lindvall C
LA  - eng
PT  - Journal Article
DEP - 20101109
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein/*deficiency/genetics
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Acinar Cell/genetics/*metabolism/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Knockout
MH  - PTEN Phosphohydrolase/*deficiency/genetics
MH  - Salivary Gland Neoplasms/genetics/metabolism/pathology
MH  - Salivary Glands/drug effects/*metabolism/pathology
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Tumor Burden/drug effects
EDAT- 2010/11/11 06:00
MHDA- 2011/02/08 06:00
CRDT- 2010/11/11 06:00
PHST- 2010/11/11 06:00 [entrez]
PHST- 2010/11/11 06:00 [pubmed]
PHST- 2011/02/08 06:00 [medline]
AID - 0008-5472.CAN-10-1758 [pii]
AID - 10.1158/0008-5472.CAN-10-1758 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Nov 15;70(22):9143-52. doi: 10.1158/0008-5472.CAN-10-1758. Epub 
      2010 Nov 9.