PMID- 25220417
OWN - NLM
STAT- MEDLINE
DCOM- 20151001
LR  - 20211021
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 34
IP  - 27
DP  - 2015 Jul
TI  - Omega-3 fatty acids reduce obesity-induced tumor progression independent of 
      GPR120 in a mouse model of postmenopausal breast cancer.
PG  - 3504-13
LID - 10.1038/onc.2014.283 [doi]
AB  - Obesity and inflammation are both risk factors for a variety of cancers, 
      including breast cancer in postmenopausal women. Intake of omega-3 
      polyunsaturated fatty acids (omega-3 PUFAs) decreases the risk of breast cancer, and 
      also reduces obesity-associated inflammation and insulin resistance, but whether 
      the two effects are related is currently unknown. We tested this hypothesis in a 
      postmenopausal breast cancer model using ovariectomized, immune-competent female 
      mice orthotopically injected with Py230 mammary tumor cells. Obesity, whether 
      triggered genetically or by high-fat diet (HFD) feeding, increased inflammation 
      in the mammary fat pad and promoted mammary tumorigenesis. The presence of tumor 
      cells in the mammary fat pad further enhanced the local inflammatory milieu. 
      Tumor necrosis factor-alpha (TNF-alpha) was the most highly upregulated cytokine in 
      the obese mammary fat pad, and we observed that TNF-alpha dose-dependently stimulated 
      Py230 cell growth in vitro. An omega-3 PUFA-enriched HFD (referred to as fish oil 
      diet, FOD) reduced inflammation in the obese mammary fat pad in the absence of 
      tumor cells and inhibited Py230 tumor growth in vivo. Although some 
      anti-inflammatory effects of omega-3 PUFAs were previously shown to be mediated by 
      the G-protein-coupled receptor 120 (GPR120), the FOD reduced Py230 tumor burden 
      in GPR120-deficient mice to a similar degree as observed in wild-type mice, 
      indicating that the effect of FOD to reduce tumor growth does not require GPR120 
      in the host mouse. Instead, in vitro studies demonstrated that omega-3 PUFAs act 
      directly on tumor cells to activate c-Jun N-terminal kinase, inhibit 
      proliferation and induce apoptosis. Our results show that obesity promotes 
      mammary tumor progression in this model of postmenopausal breast cancer and that 
      omega-3 PUFAs, independent of GPR120, inhibit mammary tumor progression in obese 
      mice.
FAU - Chung, H
AU  - Chung H
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      California, La Jolla, CA, USA.
FAU - Lee, Y S
AU  - Lee YS
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      California, La Jolla, CA, USA.
FAU - Mayoral, R
AU  - Mayoral R
AD  - 1] Division of Endocrinology and Metabolism, Department of Medicine, University 
      of California, La Jolla, CA, USA [2] Biomedical Network Center for the study of 
      Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.
FAU - Oh, D Y
AU  - Oh DY
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      California, La Jolla, CA, USA.
FAU - Siu, J T
AU  - Siu JT
AD  - Department of Pathology, University of California at San Diego, La Jolla, CA, 
      USA.
FAU - Webster, N J
AU  - Webster NJ
AD  - 1] Division of Endocrinology and Metabolism, Department of Medicine, University 
      of California, La Jolla, CA, USA [2] Moores Cancer Center, University of 
      California, La Jolla, CA, USA [3] San Diego VA Healthcare System, San Diego, CA, 
      USA.
FAU - Sears, D D
AU  - Sears DD
AD  - 1] Division of Endocrinology and Metabolism, Department of Medicine, University 
      of California, La Jolla, CA, USA [2] Moores Cancer Center, University of 
      California, La Jolla, CA, USA.
FAU - Olefsky, J M
AU  - Olefsky JM
AD  - 1] Division of Endocrinology and Metabolism, Department of Medicine, University 
      of California, La Jolla, CA, USA [2] Moores Cancer Center, University of 
      California, La Jolla, CA, USA.
FAU - Ellies, L G
AU  - Ellies LG
AD  - 1] Department of Pathology, University of California at San Diego, La Jolla, CA, 
      USA [2] Moores Cancer Center, University of California, La Jolla, CA, USA.
LA  - eng
GR  - P30 CA23100/CA/NCI NIH HHS/United States
GR  - P01 DK074868/DK/NIDDK NIH HHS/United States
GR  - K22 CA118182/CA/NCI NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - P30 CA023100/CA/NCI NIH HHS/United States
GR  - I01 BX000130/BX/BLRD VA/United States
GR  - U54 CA155435/CA/NCI NIH HHS/United States
GR  - P50 HD012303/HD/NICHD NIH HHS/United States
GR  - R01 DK101395/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140915
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (FFAR4 protein, mouse)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Receptors, G-Protein-Coupled)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diet, High-Fat
MH  - Disease Progression
MH  - Fatty Acids, Omega-3/*pharmacology
MH  - Female
MH  - Mammary Neoplasms, Experimental/*complications/genetics/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Obesity/*complications/metabolism
MH  - Ovariectomy
MH  - Postmenopause/physiology
MH  - Receptors, G-Protein-Coupled/*physiology
PMC - PMC4362785
MID - NIHMS617196
EDAT- 2014/09/16 06:00
MHDA- 2015/10/02 06:00
PMCR- 2016/01/01
CRDT- 2014/09/16 06:00
PHST- 2014/04/04 00:00 [received]
PHST- 2014/06/27 00:00 [revised]
PHST- 2014/07/27 00:00 [accepted]
PHST- 2014/09/16 06:00 [entrez]
PHST- 2014/09/16 06:00 [pubmed]
PHST- 2015/10/02 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - onc2014283 [pii]
AID - 10.1038/onc.2014.283 [doi]
PST - ppublish
SO  - Oncogene. 2015 Jul;34(27):3504-13. doi: 10.1038/onc.2014.283. Epub 2014 Sep 15.