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IGF1 dependence of dietary energy balance effects on murine MET1 mammary tumor progression, epithelial-to-mesenchymal transition and chemokine expression.
MedLine Citation:
PMID:  23152442     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Luminal breast tumors with little or no estrogen receptor-α expression confer poor prognosis. Using the Met1 murine model of luminal breast cancer, we characterized the insulin-like growth factor 1 (IGF1)-dependency of diet-induced obesity (DIO) and calorie restriction (CR) effects on tumor growth, growth factor signaling, epithelial-to-mesenchymal transition (EMT) and chemokine expression. Liver-specific IGF1-deficient (LID) and littermate control (LC) mice were administered control, DIO or 30% CR diets for 3 months before orthotopic injection of Met1 cells. Tumors grew for 1 month, were excised and assessed for Akt pathway activation and mRNA expression of chemokine and EMT constituents. LID mice, regardless of diet, displayed reduced Met1 tumor growth and downregulated Akt, EMT and chemokine pathways. CR, relative to control, reduced serum IGF1 and Met1 tumor growth in LC (but not LID) mice. DIO, relative to control, increased Met1 tumor growth and chemokine expression in LID mice, and had no effect on serum IGF1 or pAkt or cyclin D1 expression in either genotype. Thus, circulating IGF1 (in association with Akt, EMT and chemokines) regulated Met1 tumor growth. While the anticancer effects of CR were largely IGF1-dependent, the procancer effects of DIO manifested only when circulating IGF1 levels were low. Thus, in a murine model of luminal breast cancer, IGF1 and its downstream signaling pathway, EMT and chemokines present possible mechanistic regulatory targets. Transplanted MMTV-1 Wnt1 mammary tumor growth was also reduced in LID mice, relative to LC mice, suggesting the IGF1 effects on mammary tumor growth are not limited to Met1 tumors.
Authors:
Nikki A Ford; Nomeli P Nunez; Valerie B Holcomb; Stephen D Hursting
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Endocrine-related cancer     Volume:  -     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
N Ford, Nutritional Sciences, University of Texas at Austin, Austin, United States.
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