Experimental manipulation of radiographic density in mouse mammary gland.
BACKGROUND
Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density.


METHODS
We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology.


RESULTS
Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density.


CONCLUSIONS
Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse.
Department of Medical Biophysics, Ontario Cancer Institute/University Health Network, Toronto, Ontario, Canada. mhariri@uhnres.utoronto.ca
Mehrdad
M
Hariri
Geoffrey A
GA
Wood
Marco A
MA
DiGrappa
Michelle
M
MacPherson
Stephanie A
SA
Backman
Martin J
MJ
Yaffe
Tak W
TW
Mak
Norman F
NF
Boyd
Rama
R
Khokha
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008321:Mammary Glands, Animal / Q000000981:diagnostic imaging* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D008327:Mammography; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
C111417:Fam89b protein, mouse; D008565:Membrane Proteins; D011991:Receptors, Virus; D025521:Tumor Suppressor Proteins; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse