PMID- 22216254
OWN - NLM
STAT- MEDLINE
DCOM- 20120521
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 12
DP  - 2011
TI  - Apc mutation enhances PyMT-induced mammary tumorigenesis.
PG  - e29339
LID - 10.1371/journal.pone.0029339 [doi]
LID - e29339
AB  - The Adenomatous Polyposis Coli (APC) tumor suppressor gene is silenced by 
      hypermethylation or mutated in up to 70% of human breast cancers. In mouse 
      models, Apc mutation disrupts normal mammary development and predisposes to 
      mammary tumor formation; however, the cooperation between APC and other mutations 
      in breast tumorigenesis has not been studied. To test the hypothesis that loss of 
      one copy of APC promotes oncogene-mediated mammary tumorigenesis, Apc(Min/+) mice 
      were crossed with the mouse mammary tumor virus (MMTV)-Polyoma virus middle T 
      antigen (PyMT) or MMTV-c-Neu transgenic mice. In the PyMT tumor model, the 
      Apc(Min/+) mutation significantly decreased survival and tumor latency, promoted 
      a squamous adenocarcinoma phenotype, and enhanced tumor cell proliferation. In 
      tumor-derived cell lines, the proliferative advantage was a result of increased 
      FAK, Src and JNK signaling. These effects were specific to the PyMT model, as no 
      changes were observed in MMTV-c-Neu mice carrying the Apc(Min/+) mutation. Our 
      data indicate that heterozygosity of Apc enhances tumor development in an 
      oncogene-specific manner, providing evidence that APC-dependent pathways may be 
      valuable therapeutic targets in breast cancer. Moreover, these preclinical model 
      systems offer a platform for dissection of the molecular mechanisms by which APC 
      mutation enhances breast carcinogenesis, such as altered FAK/Src/JNK signaling.
CI  - (c) 2011 Prosperi et al.
FAU - Prosperi, Jenifer R
AU  - Prosperi JR
AD  - Department of Surgery, University of Chicago, Chicago, Illinois, USA.
FAU - Khramtsov, Andrey I
AU  - Khramtsov AI
FAU - Khramtsova, Galina F
AU  - Khramtsova GF
FAU - Goss, Kathleen H
AU  - Goss KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111222
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/*immunology
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - *Genes, APC
MH  - Mammary Neoplasms, Experimental/*genetics/pathology/virology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - *Mutation
MH  - Wnt Proteins/metabolism
MH  - beta Catenin/metabolism
PMC - PMC3245255
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/01/05 06:00
MHDA- 2012/05/23 06:00
PMCR- 2011/12/22
CRDT- 2012/01/05 06:00
PHST- 2011/08/26 00:00 [received]
PHST- 2011/11/26 00:00 [accepted]
PHST- 2012/01/05 06:00 [entrez]
PHST- 2012/01/05 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
PHST- 2011/12/22 00:00 [pmc-release]
AID - PONE-D-11-16666 [pii]
AID - 10.1371/journal.pone.0029339 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(12):e29339. doi: 10.1371/journal.pone.0029339. Epub 2011 Dec 22.