PMID- 12602920
OWN - NLM
STAT- MEDLINE
DCOM- 20030501
LR  - 20220408
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 77
IP  - 3
DP  - 2003 Feb
TI  - Genetically obese MMTV-TGF-alpha/Lep(ob)Lep(ob) female mice do not develop 
      mammary tumors.
PG  - 205-15
AB  - Elevated body weight is a risk factor for postmenopausal breast cancer and is 
      associated with increased incidence of spontaneous and chemically induced mammary 
      tumors (MTs) in rodents. In this study, genetically obese Lep(ob)Lep(ob) female 
      mice that overexpress human TGF-alpha (transforming growth factor-alpha) were 
      used to assess the role of body weight on oncogene-induced MT development in 
      comparison to lean counterparts. MMTV (mouse mammary tumor virus)-TGF-alpha and 
      Lep strain mice were crossed to produce TGF-alpha/Lep(+)Lep(+) (homozygous lean), 
      TGF-alpha/Lep(+)Lep(ob) (heterozygous lean) and TGF-alpha/Lep(ob)Lep(ob) 
      (homozygous obese) genotypes. Body weights were determined weekly and mice 
      palpated for the presence of MTs until 104 weeks of age. Despite their 
      significantly higher body weight, obese TGF-alpha/Lep(ob)Lep(ob) mice failed to 
      develop MTs. MTs were detected between 48 and 104 weeks of age for 26/39 
      TGF-alpha/Lep(+)Lep(ob) mice and for 19/38 TGF-alpha/Lep(+)Lep(+) mice between 67 
      and 104 weeks of age. Although MT incidence was not statistically different 
      between the lean groups, age of MT detection tended to be younger for 
      TGF-alpha/Lep(+)Lep(ob) mice (p < 0.09). There were significant effects of both 
      genotype and MTs on final body weight, that is, TGF-alpha/Lep(+)Lep(ob) mice 
      weighed more than homozygous lean mice, and mice with MTs weighed more than those 
      without MTs. TGF-alpha/Lep(ob)Lep(ob) mice are not a good model to evaluate the 
      effect of body weight on MT development possibly due to leptin deficiency. 
      However, the finding that increased body weight is associated with increased 
      oncogene-induced MT development within the normal weight range provides 
      experimental support for the role of body weight in breast cancer.
FAU - Cleary, Margot P
AU  - Cleary MP
AD  - The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. 
      mpcleary@hi.umn.edu
FAU - Phillips, Frederick C
AU  - Phillips FC
FAU - Getzin, Susan C
AU  - Getzin SC
FAU - Jacobson, Tina L
AU  - Jacobson TL
FAU - Jacobson, Michelle K
AU  - Jacobson MK
FAU - Christensen, Trace A
AU  - Christensen TA
FAU - Juneja, Subhash C
AU  - Juneja SC
FAU - Grande, Joseph P
AU  - Grande JP
FAU - Maihle, Nita J
AU  - Maihle NJ
LA  - eng
GR  - CA69655/CA/NCI NIH HHS/United States
GR  - DK16105/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (DNA Primers)
RN  - 0 (Leptin)
RN  - 0 (Transforming Growth Factor alpha)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - DNA Primers
MH  - Disease Models, Animal
MH  - Female
MH  - Leptin/genetics
MH  - Mammary Neoplasms, Experimental/*genetics/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Inbred C57BL/genetics
MH  - Mice, Obese/genetics
MH  - Obesity/*genetics
MH  - Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Transforming Growth Factor alpha/genetics
EDAT- 2003/02/27 04:00
MHDA- 2003/05/02 05:00
CRDT- 2003/02/27 04:00
PHST- 2003/02/27 04:00 [pubmed]
PHST- 2003/05/02 05:00 [medline]
PHST- 2003/02/27 04:00 [entrez]
AID - 10.1023/a:1021891825399 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2003 Feb;77(3):205-15. doi: 10.1023/a:1021891825399.