EBM Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cleary, M. P.
Right arrow Articles by Maihle, N. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cleary, M. P.
Right arrow Articles by Maihle, N. J.
Experimental Biology and Medicine 229:182-193 (2004)
© 2004 Society for Experimental Biology and Medicine

ORIGINAL RESEARCH ARTICLE

Leptin Receptor–Deficient MMTV-TGF-{alpha}/LeprdbLeprdb Female Mice Do Not Develop Oncogene-Induced Mammary Tumors

Margot P. Cleary*,1, Subhash C. Juneja{dagger}, Frederick C. Phillips*, Xin Hu*, Joseph P. Grande{ddagger} and Nita J. Maihle{ddagger},2

* Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, Minnesota 55912; and Departments of {dagger} Laboratory Medicine and Pathology and {ddagger} Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905

To whom requests for reprints should be addressed at 1 Hormel Institute, University of Minnesota, 801 16th Avenue N.E., Austin, MN 55912. E-mail: mpcleary{at}hi.umn.edu

Being overweight is a risk factor for postmenopausal breast cancer and is associated with an increased incidence and shortened latency of spontaneous and chemically induced mammary tumors in rodents. However, leptin-deficient obese LepobLepob female mice have reduced incidences of spontaneous and oncogene-induced mammary tumors. Of interest, leptin enhances the proliferation of human breast cancer cell lines in which leptin receptors are expressed, which suggests that leptin signaling plays a role in tumor development. We evaluated oncogene-induced mammary tumor development in obese MMTV-TGF-{alpha}/LeprdbLeprdb mice that exhibit a defect in OB-Rb, which is considered to be the major signaling isoform of the leptin receptor. Lepr and MMTV-TGF-{alpha} mice were crossed, and the offspring were genotyped for oncogene expression and the determination of Lepr status. Lean MMTV-TGF-{alpha}/Lepr+Lepr+ (homozygous) and MMTV-TGF-{alpha}/Lepr+Leprdb (heterozygous) mice and obese MMTV-TGF-{alpha}/LeprdbLeprdb mice were monitored until age 104 weeks. Body weights of MMTV-TGF-{alpha}/ LeprdbLeprdb mice were significantly heavier than those of the lean groups. No mammary tumors were detected in MMTV-TGF-{alpha}/LeprdbLeprdb mice, whereas the incidence of mammary tumors in MMTV-TGF-{alpha}/Lepr+Lepr+ and MMTV-TGF-{alpha}/ Lepr+Leprdb mice was 69% and 82%, respectively. Examination of mammary tissue whole mounts indicated an absence of duct formation and branching for MMTV-TGF-{alpha}/LeprdbLeprdb mice. Both age at mammary tumor detection and tumor burden (tumors/mouse and tumor weights) were similar for the lean genotypes. Serum leptin levels of MMTV-TGF-{alpha}/LeprdbLeprdb mice were 12–20-fold higher than levels of lean mice. Thus, despite elevated serum leptin levels, leptin receptor–deficient MMTV-TGF-{alpha}/LeprdbLeprdb mice do not develop mammary tumors. This study provides additional evidence that leptin and its cognate receptor may be involved in mammary tumorigenesis.

Key Words: leptin • leptin receptor • breast cancer • mice • obesity • OB-Rb




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
D. R. Cochrane, N. S. Spoelstra, E. N. Howe, S. K. Nordeen, and J. K. Richer
MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents
Mol. Cancer Ther., May 1, 2009; 8(5): 1055 - 1066.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Johansson, S. Gandini, A. Guerrieri-Gonzaga, S. Iodice, M. Ruscica, B. Bonanni, M. Gulisano, P. Magni, F. Formelli, and A. Decensi
Effect of Fenretinide and Low-Dose Tamoxifen on Insulin Sensitivity in Premenopausal Women at High Risk for Breast Cancer
Cancer Res., November 15, 2008; 68(22): 9512 - 9518.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. N Perera, H. G Chin, N. Duru, and I. G Camarillo
Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression
J. Endocrinol., November 1, 2008; 199(2): 221 - 233.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
C. N. Perera, H. S. Spalding, S. I. Mohammed, and I. G. Camarillo
Identification of Proteins Secreted from Leptin Stimulated MCF-7 Breast Cancer Cells: A Dual Proteomic Approach
Experimental Biology and Medicine, June 1, 2008; 233(6): 708 - 720.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
L. G. Bermudez-Humaran, S. Nouaille, V. Zilberfarb, G. Corthier, A. Gruss, P. Langella, and T. Issad
Effects of Intranasal Administration of a Leptin-Secreting Lactococcus lactis Recombinant on Food Intake, Body Weight, and Immune Response of Mice
Appl. Envir. Microbiol., August 15, 2007; 73(16): 5300 - 5307.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
L. Vona-Davis and D. P Rose
Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression
Endocr. Relat. Cancer, June 1, 2007; 14(2): 189 - 206.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. K. Saxena, P. M. Vertino, F. A. Anania, and D. Sharma
Leptin-induced Growth Stimulation of Breast Cancer Cells Involves Recruitment of Histone Acetyltransferases and Mediator Complex to CYCLIN D1 Promoter via Activation of Stat3
J. Biol. Chem., May 4, 2007; 282(18): 13316 - 13325.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Mauro, S. Catalano, G. Bossi, M. Pellegrino, I. Barone, S. Morales, C. Giordano, V. Bartella, I. Casaburi, and S. Ando
Evidences that Leptin Up-regulates E-Cadherin Expression in Breast Cancer: Effects on Tumor Growth and Progression
Cancer Res., April 1, 2007; 67(7): 3412 - 3421.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
M. P. Cleary, X. Hu, M. E. Grossmann, S. C. Juneja, S. Dogan, J. P. Grande, and N. J. Maihle
Prevention of Mammary Tumorigenesis by Intermittent Caloric Restriction: Does Caloric Intake During Refeeding Modulate the Response?
Experimental Biology and Medicine, January 1, 2007; 232(1): 70 - 80.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. R. Gonzalez, S. Cherfils, M. Escobar, J. H. Yoo, C. Carino, A. K. Styer, B. T. Sullivan, H. Sakamoto, A. Olawaiye, T. Serikawa, et al.
Leptin Signaling Promotes the Growth of Mammary Tumors and Increases the Expression of Vascular Endothelial Growth Factor (VEGF) and Its Receptor Type Two (VEGF-R2)
J. Biol. Chem., September 8, 2006; 281(36): 26320 - 26328.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Revillion, M. Charlier, V. Lhotellier, L. Hornez, S. Giard, M.-C. Baranzelli, J. Djiane, and J.-P. Peyrat
Messenger RNA expression of leptin and leptin receptors and their prognostic value in 322 human primary breast cancers.
Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2088 - 2094.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the Society for Experimental Biology and Medicine.